RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63/014,283, filed on Apr. 23, 2020, the entire contents of which is expressly incorporated herein by reference.
BACKGROUND OF THE INVENTION Gene-based neurotherapeutics holds great therapeutic potential. Clinical efficacy has already been obtained for central nervous system (CNS) diseases and eye disease through Adeno Associated Virus (AAV) gene therapy. The general lack of current effective neurotherapies for many devastating neurologic diseases portends great future demands for AAV gene-based neurotherapy.
Efficient and specific delivery to a target organ, such as the brain, is a rate limiting step in many protein-based therapeutics. There are multiple barriers to efficient direct protein delivery to the CNS.
One of the great challenges lies in the blood-brain barrier (BBB). Unlike the vasculature in other organ systems, the brain endothelium forms intercellular tight junctions (TJs) that limit greatly the paracellular access of blood-borne components to the tissue parenchyma. As a consequence of this “physical barrier” generated by TJs, gene transfer vehicles attempting entry into the CNS are forced to go through the transcellular route. There, however, specialized lumen facing efflux transporters, which include both the ABC family of transporters and multidrug resistance-related proteins, contribute to the formation of the “transport barrier” that prevents xenobiotic substances from gaining access to the neuronal environment. Another obstacle that partially prevents endothelial crossing of gene-therapy vehicles is the trancytotic/endosomal sorting, which can lead to degradation. Although the endothelium is the greatest obstacle in restricting access to the CNS, the presence of a complex extracellular space, molecular composition and geometry also significantly impede diffusion of viral-based gene delivery systems. That is, even if a therapy can be designed to target one of these receptors and traverse the BMVEC cytoplasm to be released at the basal cell membrane, only the first of many guardian mechanisms at the BBB has been overcome. If neurons are the target cell type, once the BBB endothelium has been passed, the basal lamina, pericytes, microglial ramifications, and the glial limitans comprised of astrocytic endfeet still have to be navigated before surpassing all of the checkpoints at the BBB and encountering a neuron.
As a result, intravascular administration of most viral vectors with the exception of few AAV serotypes has proven unsuccessful in the treatment of neurological diseases, potentially because these gene delivery platforms cannot negotiate their way across the BBB to access their target cells.
Another challenge lies in the promoters used in the gene therapy vectors. With the discovery of new viral vectors, mainly AAV capsids, with remarkable CNS tropism after vascular, CSF administration, or direct intracranial injection, the field of AAV mediated CNS gene therapy is accelerating rapidly towards clinical trials in a number of neurological diseases, and the expedient approach has been to use specific promoters with a proven track record of mediating long-term gene expression given the serious nature of many of these diseases, many of which are pediatric.
The majority of the pre-clinical studies have used strong ubiquitous promoters to provide a broad overview of transgene expression in different tissues and cell types throughout the body after intravascular infusions, or CNS cell types after intracranial delivery.
The CAG/CBA/CB promoter is generally viewed as a ubiquitous promoter as it works in numerous tissues and cell types. However, the assumption that it is highly active in every cell type may not be entirely warranted in the CNS. Studies have been conducted using AAV vectors with the same capsid but carrying different CNS cell specific promoters or the CBA promoter. The apparent discrepancy in CNS transduction profiles of these different AAV vectors suggests that the CBA promoter may not mediate detectable transgene expression in all cell types in the brain. Additional experiments have been conducted using AAV vectors with numerous tropism carrying the cytomegalovirus (CMV), CBA, Rous sarcoma virus (RSV), or human GUSB promoters to drive transgene expression, in the context of intra-parenchymal delivery to different brain structures.
In clinical studies, the majority of AAV vectors for treating neurological diseases have used the CMV immediate early promoter followed by a chimeric intron composed of a CMV splice donor and a human globin splice acceptor, or a version of the CAG/CBA promoter (supra). Two other clinical trials have tested AAV vectors carrying mammalian promoters such as the mouse phosphoglycerate kinase (PGK) promoter, or the rat neuron-specific enolase (NSE) promoter. The choice of promoters is based on the availability of extensive data from pre-clinical studies in different animal models showing that AAV-mediated transgene expression under these promoters is stable and long lasting in the mammalian brain. The stability of AAV gene expression in the human brain has been evaluated in clinical trials using an AAV2 vector encoding aromatic amino acid decarboxylase (AADC) injected into the putamen of Parkinson's disease patients, or children afflicted with AADC deficiency.
An indisputable fact about these AAV-CMV or AAV-CAG/CBA vectors is their ability to drive strong gene expression in many neurons in the CNS of multiple species. The disparate CNS transduction results between cellular promoters and strong non-mammalian promoters raises the possibility that the current generation of AAV vectors express transgenes at exceptionally high levels in a small percentage of all cells that harbor transcriptionally ready vector genomes in the nucleus. A recent report documented considerable toxicity in non-human primates (NHPs) receiving intraparenchymal injections of an AAV2 vector encoding human acid sphingomyelinase. Another safety study on intracranial delivery of an AAVrh10 vector encoding human tripeptidyl peptidase (TPP-I) in NHPs reported white matter edema and inflammation. The interpretation of these results is complicated, but a possible interpretation of the results is that these inflammatory responses are secondary to protein expression overload and non-specific expression in AAV transduced neurons.
The potential for toxicity due to excessive transgene expression is particularly acute in neurological diseases where the expressed proteins are not secreted, and thus the need for high level expression is even less. In one particular case, the development of an AAV gene therapy approach for Rett syndrome represents a significant challenge to the prevalent approach of simply using strong promoters. This disease is caused by mutations in the MeCP2 gene on the X-chromosome. Interestingly, duplication of this gene also leads to neurodevelopmental delays, suggesting that expression of this gene in the CNS need to be tightly controlled, which is a challenge to current AAV gene therapy.
SUMMARY OF THE INVENTION The invention described herein provides a gene replacement therapy platform to replace mutated genes by AAV Gene Therapy.
According to the invention described herein, about 40 exemplary central nervous system (CNS) disease drug protypes are packaged in recombinant AAV vectors for intravenous administration to a patient, in order to express functional genes in native neuronal cells. The technology is designed for intravenous dosing of AAV to express genes precisely in intended cell types by using endogenous/native promoter fused with viral/heterologous enhancer.
In an exemplary embodiment, the gene cassette in the AAV vector of the invention begins with AAV inverted terminal repeat (ITR), followed by proprietary heterologous enhancer, followed by a native promoter of a gene of interest (GOI), 5′UTR, proprietary codon optimized gene of interest (GOI), 3′UTR, and ends in another AAV inverted terminal repeat (ITR).
Thus one aspect of the invention provides a recombinant adeno-associated viral (rAAV) vector, comprising: (1) a polynucleotide comprising a gene of interest (GOI), under the transcriptional control of the native/endogenous promoter of said GOI; (2) a heterologous enhancer that enhances transcription of the GOI from the native/endogenous promoter; and, (3) a pair of inverted terminal repeat (ITR) flanking the polynucleotide.
In certain embodiments, the GOI is a neuronal gene, or is a gene expressed in neuronal tissues (CNS and/or PNS).
In certain embodiments, the GOI is defective (e.g., loss-of-function) in a neuronal disease or condition.
In certain embodiments, the neuronal disease or condition is a CNS disease or condition.
In certain embodiments, the CNS disease or condition is: Ceroid-Lipofuscinosis, Fucosidosis, Giant Axonal Neuropathy, Globoid cell leukodystrophy, Mucolipidiosis Type IV, Neuronal Ceroid Lipofusinoses, Niemann-Pick Disease, Sandhoff Disease, Sanfilippo syndrome, Tay-Sachs Disease, Hunter Syndrome, Sialidosis, Multiple Sulfatase Deficiency, Childhood Epilepsy, CMT Peripheral Neuropathy, Neuronal Ceroid Lipofusinoses, Aspartylglycosaminuria, Mucopolysaccharidoses, Parkinsons Disease/Symptoms, GM1-Gangliosidosis, Charcot-Marie-Tooth Type 1A, Retts Syndrome, Dannon Disease, Mucopolysaccharidoses (due to GNS, HGSNAT, NAGLU, or ARSB), Sly Syndrome, Biotin basal ganglia disease, Pelizaeus-Merzbacher disease, Neuronal Ceroid Lipofusinoses, Canavan Disease, Beta-Mannosidosis, Wolman Disease, Cystinosis, Alzheimer's Disease/Symptom, Salla Disease, Jansky-Bielschowsky disease, Neuronal ceroid lipofuscinoses, or GM2 gangliosidosis.
In certain embodiments, the GOI is: CLN3, FUCA1, GAN, GALC, MCOLN1, PPT1, SMPD1, HEXB, SGSH, HEXA, IDS, NEU1, SUMF1, GAT1/SLCA1, FIG. 4, CLN5, AGA, IDUA, GDNF, GLB1, PMP22/MFN2, MECP2, LAMP2, NAGLU, ARSB, GUSB, SLC19A3, PLP1, TPP1/CLN2, ACY2/ASPA, MANBA, LIPA, CTNS, GNS, HGSNAT, NEUROD1, SLC17A5, CLN6, CLN8, or GM2A.
In certain embodiments, the rAAV has a tropism for neuronal cells, or for a cell in neuronal tissue.
In certain embodiments, the rAAV is AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 or rAAVrh.10, preferably AAV9.
In certain embodiments, the rAAV comprises AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 and rAAVrh.10 capsids, preferably AAV9 capsids.
In certain embodiments, the polynucleotide further comprises a 5′-UTR coding region, and a 3′-UTR coding region.
In certain embodiments, the heterologous enhancer is a viral enhancer.
In certain embodiments, the viral enhancer is CMV enhancer.
In certain embodiments, the viral enhancer is SV-40 enhancer.
In certain embodiments, the heterologous enhancer comprises a polynucleotide of SEQ ID NO: 1.
Another aspect of the invention provides a pharmaceutical composition comprising any one of the rAAV vector of the invention.
In certain embodiments, the pharmaceutical composition is formulated for intravenous administration (e.g., to the blood) or intrathecal administration (e.g., to spinal fluid).
Another aspect of the invention provides a cell infected with any one of the rAAV vector of the invention.
Another aspect of the invention provides a recombinant AAV virus comprising any one of the rAAV vector of the invention, wherein the serotype or pseudotype of the recombinant AAV virus is for preferential infection of a neuronal cell or a cell in neuronal tissue.
Another aspect of the invention provides a method of treating a (genetic) disease or disorder in a subject, the method comprising administering the recombinant AAV virus of the invention into the subject.
In certain embodiments, the genetic disease or disorder is a neuronal disease or disorder, and/or wherein the recombinant AAV virus preferentially infects a neuronal cell or a cell in neuronal tissue of the subject, thereby treating the neuronal disease or disorder.
In certain embodiments, the rAAV virus is administered to the subject intravenously or intrathecally.
Another aspect of the invention provides a method of producing any one of the rAAV vector of the invention, the method comprising introducing any one of the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.
In certain embodiments, the rep/cap proteins comprise one or more AAV9 capsid proteins.
It should be understood that any one embodiment of any one of the aspects of the invention above, including specific embodiments described only in one section of the application, can be combined with one or more additional embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic drawing (not to scale) showing a generic structure of the subject rAAV vector, as well as an intended mode of action for the vector. The Gene of Interest (GOI) is put under the control of its native promoter. Transcription from the native promoter is further enhanced by the presence of a powerful enhancer, such as a viral enhancer like CMV enhancer, to facilitate the expression of the GOI in the native cells such GOI is normally expressed. The entire recombinant sequence is flanked by two AAV ITR sequences, such as AAV9 ITR sequences for the preferred neuronal cell tropism.
FIG. 2 is a gel image confirming the construction of rAAV viral vectors comprising a number of representative GOI's that are defective in neuronal diseases/disorders. Also shown is a rAAV vector encoding a GFP reporter gene, which can be switched out by any of the GOI's.
FIG. 3 is a gel image confirming the construction of additional rAAV viral vectors comprising a number of representative GOI' s that are defective in neuronal diseases/disorders.
DETAILED DESCRIPTION OF THE INVENTION 1. Overview The invention described herein provides methods and compositions for using recombinant viral vectors, such as AAV-based viral vectors or lentiviral vectors to express any gene-of-interest (GOI) under the control of its native promoter so that the GOI is preferentially and exclusively expressed in the cells the GOI is intended to be expressed. The GOI is further under the transcriptional control of a powerful heterologous enhancer, such as a viral enhancer like CMV enhancer, which further boosts the transcription and expression of the GOI. Therefore, after a single intravenous treatment, the protein product of interest is expressed at high levels only in the endogenous/native cell types, thereby improving therapeutic safety and efficacy.
Thus in one aspect, the invention described herein provides a recombinant adeno-associated viral (rAAV) vector, comprising: (1) a polynucleotide comprising a gene of interest (GOI), under the control of the native/endogenous promoter of said GOI; (2) a heterologous enhancer that enhances transcription of the GOI from the native/endogenous promoter; and, (3) a pair of inverted terminal repeat (ITR) flanking the polynucleotide.
In certain embodiments, the GOI is a neuronal gene.
In certain embodiments, the neuronal gene is defective (e.g., loss-of-function) in a neuronal disease or condition.
In certain embodiments, the neuronal disease or condition is a CNS disease or condition.
In certain embodiments, the CNS disease or condition is: Ceroid-Lipofuscinosis, Fucosidosis, Giant Axonal Neuropathy, Globoid cell leukodystrophy, Mucolipidiosis Type IV, Neuronal Ceroid Lipofusinoses, Niemann-Pick Disease, Sandhoff Disease, Sanfilippo syndrome, Tay-Sachs Disease, Hunter Syndrome, Sialidosis, Multiple Sulfatase Deficiency, Childhood Epilepsy, CMT Peripheral Neuropathy, Neuronal Ceroid Lipofusinoses, Aspartylglycosaminuria, Mucopolysaccharidoses, Parkinsons Disease/Symptoms, GM1-Gangliosidosis, Charcot-Marie-Tooth Type 1A, Retts Syndrome, Dannon Disease, Mucopolysaccharidoses (due to GNS, HGSNAT, NAGLU, or ARSB), Sly Syndrome, Biotin basal ganglia disease, Pelizaeus-Merzbacher disease, Neuronal Ceroid Lipofusinoses, Canavan Disease, Beta-Mannosidosis, Wolman Disease, Cystinosis, Alzheimer's Disease/Symptom, Salla Disease, Jansky-Bielschowsky disease, Neuronal ceroid lipofuscinoses, or GM2 gangliosidosis.
In certain embodiments, the GOI is: CLN3, FUCA1, GAN, GALC, MCOLN1, PPT1, SMPD1, HEXB, SGSH, HEXA, IDS, NEU1, SUMF1, GAT1/SLCA1, FIG. 4, CLN5, AGA, IDUA, GDNF, GLB1, PMP22/MFN2, MECP2, LAMP2, NAGLU, ARSB, GUSB, SLC19A3, PLP1, TPP1/CLN2, ACY2/ASPA, MANBA, LIPA, CTNS, GNS, HGSNAT, NEUROD1, SLC17A5, CLN6, CLN8, or GM2A.
In certain embodiments, the rAAV has a tropism for neuronal cells. In certain embodiment, the rAAV serotype is, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 or rAAVrh.10.
In certain embodiments, the rAAV serotype is AAV9. In certain embodiments, the rAAV has a pseudotype of xxx. In certain embodiments, the polynucleotide further comprises a 5′-UTR coding region, and a 3′-UTR coding region.
In certain embodiments, the heterologous enhancer is a viral enhancer.
In certain embodiments, the viral enhancer is CMV enhancer.
In certain embodiments, the viral enhancer is SV40 enhancer.
Another aspect of the invention provides a pharmaceutical composition comprising the rAAV vector of the invention.
In certain embodiments, the pharmaceutical composition is formulated for intravenous administration.
Another aspect of the invention provides a cell infected with the rAAV vector of the invention.
Another aspect of the invention provides a recombinant AAV virus comprising the rAAV vector of the invention, wherein the serotype or pseudotype of the recombinant AAV virus is for preferential infection of a neuronal cell.
Another aspect of the invention provides a method of treating a (genetic) disease or disorder in a subject, the method comprising introducing the recombinant AAV virus of the invention into the subject.
In certain embodiments, the genetic disease or disorder is a neuronal disease or disorder, the recombinant AAV virus preferentially infects a neuronal cell of the subject, and treats the neuronal disease or disorder.
Another aspect of the invention provides a method of producing the rAAV vector of the invention, comprising introducing the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.
With the general aspects of the invention described, further detailed embodiments of the invention are provided below.
2. Treatable Disease or Conditions The recombinant AAV vector and recombinant AAV virus of the invention, together with the pharmaceutical composition comprising the same, can be used to treat a number of diseases and conditions, particularly neuronal diseases or indications treatable by gene therapy.
Diseases or conditions treatable by the AAV vector/virus/method of the invention are typically characterized by lacking a functional neuronal protein or enzyme, which neuronal diseases or indications can be alleviated (if not cured), treated, or prevented (e.g., at least the onset is delayed), by providing functional versions of the proteins or enzymes. The externally provided functional versions of the proteins or enzymes may be identical in sequence to the wild-type proteins or enzymes that are lacking in a host having such diseases or conditions, or may be a variant of the wild-type proteins or enzymes.
In certain embodiments, the neuronal diseases or conditions can be treated by introducing into the host the subject AAV virus that will infect target host (neuronal) tissues, and stably express the encoded GOI that is defective in the diseases or conditions throughout the life span of the host. The subject AAV virus may only need to be introduced into the host once, or can be introduced into the host multiple times as needed.
A few representative polynucleotide sequences of the invention encoding several genes-of-interest (GOI) are listed below. These polynucleotide sequences can be part of the subject AAV vector sequences. These sequences are for illustrative purpose only and are non-limiting.
Giant Axonal Neuropathy (GAN) Giant axonal neuropathy (GAN) is a severe, slowly progressive neurodegenerative disorder characterized by progressive motor and sensory peripheral neuropathy, central nervous system involvement (including pyramidal and cerebellar signs), and characteristic kinky hair in most cases. GAN is inherited as an autosomal recessive trait, and is associated with more than 50 different causative mutations in GAN gene (16q24.1), encoding the ubiquitously expressed cytoskeletal protein gigaxonin.
Disease prognosis varies but is usually poor. Most patients become wheelchair-dependent in the second decade of life, and eventually progress to a bedridden state in early adulthood. Secondary complications, such as respiratory failure, may occur. Life expectancy does not exceed the third decade.
Current GAN treatment is symptomatic, focusing on stimulating intellectual and physical development, as well as communication skills, through physical, occupational and speech therapy, starting from the initiation of symptoms. Skeletal deformities and ophthalmoplegia may need surgery.
Thus in one embodiment, the GOI is GAN that encodes gigaxonin, and the disease or condition treatable by the subject AAV vector/virus is Giant Axonal Neuropathy (GAN). The composition and methods of the invention can be used to produce gigaxonin expressed permanently from AAV vectors stably maintained with the host's genome as extra chromosomal material, in native neuronal cells that normally express GAN, thus effectively treating giant axonal neuropathy.
A representative polynucleotide of the invention that can be encoded by the AAV vector of the invention is described below.
(SEQ ID NO: 2)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
CTCACAGGGATACTGGGTAGGTATCATGGAGAAGA
TAAGTCCAAGCTGCTTGTCTTGTGTGTTTCTTACC
TTTTTAAATATATTTTTCGGCCGGGTGTGGTGGCT
TATGCCTGTAATTCCAGTACTTTGGGAAGCCAAGG
TGGGCGGATCACAAGGTCAGGAGTTCGATACCAGC
CTGGCCAACATGGTAAAACCCCATCTCTACTAAAG
ATGCAAAAGTTAGCCAGGCATGGTGGCACATGCCT
GTAGTCCCAGCTACTTGGGAGGCTGAGGCAGGAGA
ACCACTTGAACCCGGGAGGCGGAGGTTGCAGTGAA
CAGAGATTGCACAACTGCACTCCAGCCTGGGCAAT
AGAGGGAGACTCCATCTCAAAAAAAAAAAAGAAAG
AAGAAAATATTTTTCAACATCCACAAAAATATAGA
AACAGTACAATGAATCTCCACATCCCCATTAAACA
TCCACAACAATATAGAGACAGTACAACGAATCTCC
ACATCCCCATTACGTGGCTTTAACAATTAGTAACT
TGCGGCCACTTTTGACTCATCTACACTCCCATCTG
CTTCCCCATCCCTTTGTTTTGTTTTGAAGCAAATC
CTAGACATCTTTATCATTGCATCCGGGAACACTGA
GCTGCATTTACAGAAGAAAGTGGAAATGCATGTGT
CTTCCACAGCCGTACCCTCCCCATCTATTCTGCCC
TGAAAACAGTTAGATACTCGGATTCCTGCCAGTGA
CTCCAAAGCCTTGGCTGGTTCAGGGTAAATACCCA
AGACTTTATTGGAGCCTTTCAGTTGGTTGAAGGAC
AGTGAAAATTCCATCCTGTCTTGCCTGGAATGCTA
GCCACATTCTTCTGGTCCGGAGTCCTCATACAATT
GCTAATTTTTTAGAGGCTTATGGAGTCCCTAACGT
TTGCACAAAATGGTTGCTACATTCCACACTCCCAT
GTGCCCTGAGCAACCTCCAGGGAAACTTCAGATAC
CGTGGGGCTTGGCCTGCCAGCTGAGCTGACCCAGC
GATCCTTTCTATCACAGCTTTGATCTTCACTGGGT
TGGGAGCCTGTCTGAATCTAAACATCTGCCTCTCT
ACTGCCCACCCCTTCAGCATTTCCTAGCTCTCCCT
GAAAGGTGCAAACATGCATGCAGTTACTCAAACAG
AATATTTATCCTTAACTCCCTCTCCCTCACAATTT
CTTTTAAAACAATCCACTATTGTCTACCCCCGCCC
CCGCATCACCCTTTCATCCAGGTGCCCATTCCCTT
CTCTCTAGTCCTGCAATACCTAAGCATCGATCTGC
CTTTAGCACATCCATCCCCGCCTTATTCTCCACGC
AGGAGCTGAGTGACCTGCACAAAATCCCCTGCTAA
ATACGGTACTTCCATGGTTCTTCACCACTGCAGAA
ACCAAACTCCTTCCCACACCAAGGAGGCCCTGCAA
AATTTAAGGCCTCCTTCGGACTTCTCCAGCTTCAT
CTGCTACATCTCCTTCCTAGCCCGCAACCAAAACC
ATCTTTTCCGGGTCTGTTTTCTCGGGTTTTTGTCC
TCTCACCTGGGCAGCTCCTTTTCTCTCATAAATAA
AGAAAGCTACAGCGACTTCGCCCTTGCTTCCATGC
ATCATCTCATGAGTCCACAACAACACTAAGAATTC
GCTTTCATTTTGCAGACGGAGAAACTGAGGATGGG
CACCTTACCCATGGCCACAGAGCTAGTAAGTGGAA
CAGCTGCAACCAGGATTCAAACTCGCGGCTCCAGA
GGCCACAGGCTTAACCACGGAATCCTAGCCCGCCC
GCACATCCCTCCATCGCGGGAGCGACCTATCTCAT
CCGTAGACACCTTCCGCTGCACCCAGCCGCAGCTG
GTCAGGCGGGCGGAGGAAGGAGGCTTCTGATTGGC
CATCTCCAGCAGCGGAGGCGAGAAGGCGGGGAGCG
ACGGTGCGGGGGCGTCGCGGAGAAATGACTTCATG
ACGCGGCTTCTTAAAGGCGCCGGCCCAGCGCGCCG
CGGA
ATGGCTGAGGGAAGTGCGGTCTCAGACCCCCAACA
CGCTGCAAGACTTCTGCGAGCTCTCTCATCTTTCA
GAGAGGAGTCACGCTTCTGTGACGCACACTTGGTC
CTTGACGGAGAAGAGATACCTGTCCAGAAAAATAT
ACTTGCCGCTGCATCCCCATACATTCGCACCAAGC
TGAACTACAATCCCCCTAAAGACGACGGGAGCACC
TATAAAATCGAATTGGAGGGCATCTCCGTGATGGT
AATGCGAGAGATACTGGATTACATATTTAGCGGCC
AGATCAGGCTGAATGAGGATACGATCCAAGATGTT
GTACAGGCAGCGGACTTGCTGCTTCTGACGGACCT
TAAGACCCTTTGCTGCGAGTTCCTCGAAGGGTGTA
TTGCTGCCGAGAATTGTATCGGAATACGAGACTTC
GCACTCCATTACTGCCTTCACCACGTTCATTACCT
TGCGACAGAGTATTTGGAAACACATTTCCGCGACG
TTAGCTCTACAGAGGAATTTCTCGAACTTAGTCCT
CAAAAGCTCAAGGAGGTTATTAGTCTTGAAAAGCT
CAACGTCGGAAATGAGCGGTACGTGTTTGAGGCCG
TGATACGGTGGATCGCCCACGACACCGAGATCCGC
AAGGTCCACATGAAGGATGTAATGTCAGCGCTGTG
GGTATCCGGTCTTGACTCTTCATACTTGAGAGAGC
AGATGCTCAACGAACCTTTGGTGAGGGAAATAGTG
AAGGAGTGTAGTAACATCCCCCTCAGCCAACCCCA
GCAAGGCGAAGCGATGCTCGCGAACTTCAAGCCCC
GAGGCTACAGCGAATGCATAGTAACAGTGGGAGGT
GAAGAACGGGTCTCCCGGAAACCCACTGCGGCGAT
GCGGTGTATGTGTCCCCTGTATGATCCCAATCGCC
AACTTTGGATCGAGCTGGCGCCGCTGTCTATGCCA
CGAATAAATCACGGGGTTCTTTCAGCCGAGGGGTT
TCTGTTCGTCTTTGGAGGGCAGGATGAGAACAAAC
AAACACTCTCCAGTGGGGAGAAATACGACCCCGAT
GCAAACACTTGGACAGCTCTGCCACCGATGAACGA
AGCCCGACACAACTTTGGTATAGTCGAAATCGACG
GTATGCTGTATATCCTTGGAGGAGAGGACGGAGAA
AAAGAACTCATCTCCATGGAATGTTACGACATTTA
CAGCAAAACTTGGACAAAGCAACCCGACCTTACTA
TGGTGAGGAAGATAGGATGTTATGCGGCAATGAAG
AAAAAGATATACGCCATGGGAGGCGGTTCTTATGG
TAAGCTCTTCGAGAGTGTGGAGTGTTATGACCCTC
GAACGCAGCAATGGACAGCCATATGTCCCCTGAAG
GAACGGCGATTTGGGGCGGTAGCGTGTGGAGTTGC
AATGGAGTTGTACGTTTTCGGAGGTGTTCGAAGTC
GGGAGGACGCGCAAGGGTCAGAGATGGTCACATGT
AAAAGCGAATTTTATCATGACGAATTTAAGCGGTG
GATTTATCTGAACGACCAAAACCTCTGTATTCCAG
CTTCCAGTTCCTTCGTATACGGCGCTGTGCCAATA
GGTGCGTCAATTTACGTCATAGGCGACTTGGACAC
TGGTACTAATTATGATTACGTACGCGAGTTTAAGA
GGAGTACAGGCACCTGGCACCACACAAAACCGCTG
CTCCCGTCCGATCTGCGAAGGACAGGTTGCGCTGC
ATTGAGGATTGCTAACTGCAAACTTTTCCGCCTGC
AACTTCAGCAAGGGCTTTTCCGCATACGAGTCCAC
AGTCCTGACTATAAAGATGACGACGACAAATA
In the sequence herein, double underlined sequences represent proprietary viral enhancer sequences (SEQ ID NO: 1, see below); bold sequences are native promoter sequences for GAN; italic sequences are coding sequence for the GOI (GAN in this case); the subscripted sequences immediately 5′ and 3′ to the GOI coding sequence are 5′-UTR and 3′-UTR sequences, respectively.
The proprietary enhancer sequences (SEQ ID NO: 1) is listed below.
(SEQ ID NO: 1)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGT
ACCTTCTGAGGCGGAAAGAACCAGCGTTACATAACTTACGGTAAATGGCC
CGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACG
TATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGT
GGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATA
TGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGG
CATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
The GAN protein sequence is:
(SEQ ID NO: 3)
MAEGSAVSDPQHAARLLRALSSFREESRFCDAHLVLDGEEIPVQKNILAA
ASPYIRTKLNYNPPKDDGSTYKIELEGISVMVMREILDYIFSGQIRLNED
TIQDVVQAADLLLLTDLKTLCCEFLEGCIAAENCIGIRDFALHYCLHHVH
YLATEYLETHFRDVSSTEEFLELSPQKLKEVISLEKLNVGNERYVFEAVI
RWIAHDTEIRKVHMKDVMSALWVSGLDSSYLREQMLNEPLVREIVKECSN
IPLSQPQQGEAMLANFKPRGYSECIVTVGGEERVSRKPTAAMRCMCPLYD
PNRQLWIELAPLSMPRINHGVLSAEGFLFVFGGQDENKQTLSSGEKYDPD
ANTWTALPPMNEARHNFGIVEIDGMLYILGGEDGEKELISMECYDIYSKT
WTKQPDLTMVRKIGCYAAMKKKIYAMGGGSYGKLFESVECYDPRTQQWTA
ICPLKERRFGAVACGVAMELYVFGGVRSREDAQGSEMVTCKSEFYHDEFK
RWIYLNDQNLCIPASSSFVYGAVPIGASIYVIGDLDTGTNYDYVREFKRS
TGTWHHTKPLLPSDLRRTGCAALRIANCKLFRLQLQQGLFRIRVHSPDYK
DDDDK
Conservative changes to the protein sequence above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 conservative residue changes, or up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% conservative residue changes) that result in a functional equivalent version of the protein (e.g., that retains at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% of the wild-type enzyme activity) are also within the scope of the invention.
Likewise, in any of the nucleotide sequence encoding the protein and variants thereof, such as in SEQ ID NO: 2, nucleotide sequence changes that do not result in sequence change of the encoded protein in SEQ ID NO: 3 due to, for example, codon degeneracy, are within the scope of the invention. Further, codon optimization of any of the polynucleotide sequence for optimal expression in a specific type of host cell is also within the scope of the invention (see further details below).
Juvenile Neuronal Ceroid Lipofuscinosis (JNCL or Batten Disease) Neuronal ceroid lipofuscinosis refers to a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) made up of fats and proteins in the body's tissues. The most commonly identified mutations are in the CLN3 gene, located on the short arm of chromosome 16 (16p12.1), found in childhood or juvenile NCLs (JNCLs).
JNCL is an autosomal recessive disorder. The normal function of CLN3 gene is not presently known, but it is known to be a transmembrane protein. Studies of the yeast CLN3 ortholog which encodes Battenin have suggested that the protein may play a role in lysosomal pH homeostasis. Furthermore, recent studies have also implied the protein's role in cathepsin D deficiency; the overexpression of the defective protein appears to have significant effects on cathepsin D processing, with implications suggesting that accumulation of ATP synthase subunit C would result.
All mutations resulting in JNCL have been shown to occur at the CLN3 gene. Of the mutations known to cause JNCL, 85% result from a 1.02 kb deletion, with a loss of amino acids 154-438, while the remaining 15% appear to result from either point or frameshift mutations.
Thus in one embodiment, the GOI is CLN3, and the disease or condition treatable by the subject AAV vector/virus is JNCL. The composition and methods of the invention can be used to produce CLN3 gene product expressed permanently from AAV vectors stably maintained with the host's genome as extra chromosomal material, in native neuronal cells that normally express CLN3, thus effectively treating JNCL.
A representative polynucleotide of the invention that can be encoded by the AAV vector of the invention is described below. Specifically, the proprietary enhancer sequence is in SEQ ID NO: 1. Native CLN3 promoter is known in the art. The coding sequence for CLN3 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
CLN3-DNA (SEQ ID NO: 4)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
TTCCCCCAGGGGCGGAAGGGGCCGGATTGGTGGCT
CTGGGGTGCATCCCCTCACCTATGATTAGGCTTGC
AAAAAAGAACTTGGCTAAACTTTATATTGTGGATA
TCTGTGTCTGCCTCCCACCTTCCTGTGACTTCCTT
GATGGCAGATGCCATGTATGAAACGCTGCTGAATT
TCTAGAGCCCTGCACGTTAGTAGGATTCCATTTTC
CATCAGCTGAGTGACCTGGGAGGCACACTAGAGAG
GGCACATTTCTTTTCTTTTCTTTTCTTTTTTTTTT
TGAGACAGTCTCACTCTGTCACCCAGGCTGGAGTG
TAGTGGCGCAGTCTCAGCTCACTGCAACCTCTGCC
TCCTGGGTTCAAGTGATTCTCCTGCCTCAGCCTCC
CGAGTAGCTGGGATTACAGGTGCGTGCCACCACAC
CTGGTTAATTTTTGTATCTTTAGTAGAGACAGGGT
TTCACCATGTTAGCCAGGCTGGTTTCGAACTCCTG
ACCTCAGGTGATCTGCCCACCTTGGCCTCCCAAAG
TGCTGGGATGACAGGCATGAGCCACCACACCCAGA
CGAGAGGGCACATTTCCAACTGCATTCTGAAGGCC
TGGTGGTGAGAAAGAGCATATAGAGGTGGCACAGC
CCATAGCAGAGATGAGGCCAAGGACAAGAAGAGAA
TGCAGGATGCCGCTTTCCACCTAGAAGAAGGTAAG
GGTATGATTCCTTATTTGGAACTACATAAAGTGAC
CTTGCTCTACTTCTCTTCCCCATACCCTCCTTCTC
CCCTCCCCAGCCCCACTTTCCTATTCCAATTAGGG
CAATTCTATGAAATCACAGCATCAGAATCTTAGGC
CTTAAAATCATTTAGTCTGGCCAGGTGCAGTGGCT
CACGCCTGTAGTCCTAGCACTTTGGGAAGCCAAGG
CAGGTGGATTGCTTGAGCTCAGGAGTTTGAGGCCA
CCCTGGGCAACGTGGCAAAATCCAGTCTCTACAAA
AAACACAAAAATTAGCTGGGCACAGTGGTGCGCAC
CTGCTGTCCCAGCTACTCGGGAGGCTGAGGTGGGA
GGATCACCTGAGCCTGGGAGGTCAAGGTTGCAGCA
AACCAAGATCCTGCCACTGCACTCCAGCCTGGGCA
ACAGAGCAAAACCCTGTCAAAAAAAAAAAAAAAAT
CTGGTCTAAGCACCACCTTTGATGGAGGCAGGAAT
CCTGCAGCAGCCTGGAGCCAACCCAATGGCTCCCT
GCCTCTGGTGCTCTATTTCTTATCACCATACAGGT
CTCTAAGGTCACCTTTAGGTCTAACATTGTATGAA
TGATTGTCAGCAACTTTCCAATTTTTTTCATATAC
ATATATTTTTTTTATTTTATTTTTTACTTTTTCTT
TTTTTGAGACAGGATCTCACTCTGTCACCCAGGCT
GGAGTGCAGTGGCGTGATCATAGCTCACTGTAGCT
TCAACCTCCTGGGCACAAGTGATCCTCCCACCTCA
GCTTCCAAGGTACCTGTGACTACAGGAATGCGCCA
CCATGCCCGGCTAATTTTGTTATATATATATATAT
ATATATTTGTACCTTGGTTTTCTCATCTGTAACAC
CAGGGGTTGAAGTGCTGTGATATTTTTTGGTTCTA
GGATAATTTGGAAATAGGGATCTCTTAACATCTTG
GATACTGCCAATAGATCATTCACGAAATCCCTTTA
GATGAGTGTTATGTTTACTTAGGTCTCTAAAACAA
TTTGTAAGGTCAACAGATGGGGATAAGAATGACCT
GAAGCTGGTCGTCTTTGTTCGCAACCAGAAACAGT
CCTGCCTCAAAAAAAAAAAAAAAAAAAAGGGAGTA
GGCAGGTGGCCATATTTGTTTCTGGCAAGTGAGTG
CTGAAGGAAAGGAGCTGAAGCCTCCCACAGTCATA
ACTGGTGCTGGCAGGCTACTGTCTCGGTCTTGGGC
GCCACTGATCTAAGGTCACGGCTCTGCTTGCTGCT
CCCACCCGCTCCAGTTTAAAACCTGCGGTTCCAGG
GTTCTCCAGCCCCTCCCTTTTTCACGCTCCGAAGC
CGAGAAGGCCCAAAGCGAAGACAGAGAGGACCCGG
AAGTAGGGAAAACCTCTGAGCACGTGATGGGGGAA
CACGCGGGTGCTGT
ATGGGAGGTTGTGCTGGTTCTCGACGCCGGTTCTC
AGATAGTGAGGGGGAGGAAACGGTGCCCGAGCCTC
GGCTTCCACTTCTGGACCATCAAGGCGCTCATTGG
AAGAATGCAGTCGGGTTTTGGCTCCTCGGTCTCTG
CAACAATTTCTCTTACGTGGTCATGTTGAGCGCTG
CCCATGACATTCTTAGTCATAAAAGAACCTCAGGC
AATCAGTCCCACGTTGATCCAGGTCCAACACCTAT
TCCTCATAACTCTAGCAGCAGATTTGACTGTAATA
GTGTTAGCACAGCTGCAGTGCTGCTCGCTGATATA
CTTCCGACGCTTGTTATAAAGTTGTTGGCTCCTCT
GGGATTGCACTTGCTGCCCTATAGTCCCCGAGTCT
TGGTTTCTGGCATTTGTGCTGCCGGCTCATTTGTC
TTGGTGGCTTTCAGTCACAGTGTGGGGACCAGTCT
GTGTGGAGTCGTGTTCGCATCAATTAGCTCTGGAC
TGGGCGAAGTAACCTTCCTGTCCCTCACAGCCTTT
TATCCGCGCGCCGTAATTAGTTGGTGGTCATCTGG
AACCGGCGGCGCGGGGCTGCTCGGCGCCCTTAGCT
ACCTGGGATTGACTCAGGCGGGGTTGTCACCACAA
CAGACTCTCCTTAGCATGCTTGGCATTCCAGCCTT
GCTTCTGGCTTCTTACTTTCTGCTCCTTACGTCCC
CGGAAGCGCAGGACCCTGGCGGTGAAGAGGAGGCG
GAGTCCGCCGCTCGACAGCCACTCATTCGAACTGA
AGCTCCCGAGTCCAAACCAGGAAGCTCTTCCTCCC
TCTCCCTGCGGGAACGGTGGACAGTCTTTAAGGGA
CTGCTGTGGTACATAGTGCCTCTTGTGGTAGTGTA
TTTCGCGGAATACTTCATAAACCAGGGTCTTTTTG
AGCTTCTTTTTTTTTGGAATACAAGCCTGTCACAC
GCCCAGCAGTACCGATGGTATCAGATGCTGTACCA
GGCGGGGGTTTTCGCTAGCCGATCCTCCCTGCGGT
GCTGCAGGATTCGATTCACTTGGGCTCTCGCGTTG
CTGCAATGCTTGAACCTCGTTTTCCTTCTCGCAGA
CGTCTGGTTCGGTTTTCTCCCTAGTATCTATCTGG
TCTTTTTGATTATATTGTATGAAGGTCTTCTGGGA
GGAGCGGCATACGTGAATACTTTTCACAATATCGC
CCTTGAGACTTCCGACGAGCATCGGGAATTTGCCA
TGGCGGCGACGTGTATCTCCGATACCCTGGGTATA
AGCCTGAGTGGACTGCTCGCGCTTCCGCTCCACGA
TTTTCTGTGTCAATTGAGCGATTATAAAGATGATG
ATGACAAATA
The CLN3 protein sequence is:
(SEQ ID NO: 5)
MGGCAGSRRRFSDSEGEETVPEPRLPLLDHQGAHWKNAVGFWLLGLCNNF
SYVVMLSAAHDILSHKRTSGNQSHVDPGPTPIPHNSSSRFDCNSVSTAAV
LLADILPTLVIKLLAPLGLHLLPYSPRVLVSGICAAGSFVLVAFSHSVGT
SLCGVVFASISSGLGEVTFLSLTAFYPRAVISWWSSGTGGAGLLGALSYL
GLTQAGLSPQQTLLSMLGIPALLLASYFLLLTSPEAQDPGGEEEAESAAR
QPLIRTEAPESKPGSSSSLSLRERWTVFKGLLWYIVPLVVVYFAEYFINQ
GLFELLFFWNTSLSHAQQYRWYQMLYQAGVFASRSSLRCCRIRFTWALAL
LQCLNLVFLLADVWFGFLPSIYLVFLIILYEGLLGGAAYVNTFHNIALET
SDEHREFAMAATCISDTLGISLSGLLALPLHDFLCQLSDYKDDDDK
Conservative changes to the CLN3 protein sequence above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 conservative residue changes, or up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% conservative residue changes) that result in a functional equivalent version of the protein (e.g., that retains at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% of the wild-type enzyme activity) are also within the scope of the invention.
Likewise, in any of the nucleotide sequence encoding the protein and variants thereof, such as in SEQ ID NO: 4, nucleotide sequence changes that do not result in sequence change of the encoded protein in SEQ ID NO: 5 due to, for example, codon degeneracy, are within the scope of the invention. Further, codon optimization of any of the polynucleotide sequence for optimal expression in a specific type of host cell is also within the scope of the invention.
Numerous other neuronal diseases/disorders can be similarly treated by the constructs, AAV vectors, and methods of the invention. A representative (non-limiting) list of the treatable diseases and disorders, along with the corresponding GOI's, are provides in the table below.
Target No. Diseases Target Gene (GOI) GOI Size
1 Ceroid-Lipofuscinosis CLN3 1403
2 Fucosidosis FUCA1 1487
3 Giant Axonal Neuropathy GAN 1880
4 Globoid cell leukodystrophy GALC 2144
5 Mucolipidiosis Type IV MCOLN1 1829
6 Neuronal Ceroid Lipofusinoses PPT1 1007
7 Niemann-Pick Disease SMPD1 1982
8 Sandhoff Disease HEXB 1757
9 Sanfilippo syndrome SGSH 1595
10 Tay-Sachs Disease HEXA 1676
11 Hunter Syndrome IDS 1739
12 Sialidosis NEU1 1334
13 Multiple Sulfatase Deficiency SUMF1 941
14 Childhood Epilepsy GAT1/SLCA1 1886
15 CMT Peripheral Neuropathy FIG4 2810
16 Neuronal Ceroid Lipofusinoses CLN5 1163
17 Aspartylglycosaminuria AGA 1127
18 Mucopolysaccharidoses IDUA 2048
19 Parkinsons Disease/Symptoms GDNF 722
20 GM1-Gangliosidosis GLB1 2120
21 Charcot-Marie-Tooth Type 1A PMP22/MFN2 569
22 Retts Syndrome MECP2 1583
23 Dannon Disease LAMP2 1322
24 Mucopolysaccharidoses NAGLU 2318
25 Mucopolysaccharidoses ARSB 1688
26 Sly Syndrome GUSB 2042
27 Biotin basal ganglia disease SLC19A3 1577
28 Pelizaeus-Merzbacher disease PLP1 920
29 Neuronal Ceroid Lipofusinoses TPP1/CLN2 1778
30 Canavan Disease ACY2/ASPA 1028
31 Beta-Mannosidosis MANBA 2726
32 Wolman Disease LIPA 1286
33 Cystinosis CTNS 1289
34 Mucopolysaccharidoses GNS 1745
35 Mucopolysaccharidoses HGSNAT 1994
36 Alzheimer's Disease/Symptom NeuroD1 1157
37 Salla Disease SLC17A5 1574
38 Jansky-Bielschowsky disease CLN6 1022
39 Neuronal ceroid lipofuscinoses CLN8 947
40 GM2 gangliosidosis GM2A 668
The sequences of the above genes that can be included in the viral vectors as GOI's are provided below.
The FUCA1 protein sequence is:
(SEQ ID NO: 6)
MRAPGMRSRPAGPALLLLLLFLGAAESVRRAQPPRRYTPDWPSLDSRPLP
AWFDEAKFGVFIHWGVFSVPAWGSEWFWWHWQGEGRPQYQRFMRDNYPPG
FSYADFGPQFTARFFHPEEWADLFQAAGAKYVVLTTKHHEGFTNWPSPVS
WNWNSKDVGPHRDLVGELGTALRKRNIRYGLYHSLLEWFHPLYLLDKKNG
FKTQHFVSAKTMPELYDLVNSYKPDLIWSDGEWECPDTYWNSTNFLSWLY
NDSPVKDEVVVNDRWGQNCSCHHGGYYNCEDKFKPQSLPDHKWEMCTSID
KFSWGYRRDMALSDVTEESEIISELVQTVSLGGNYLLNIGPTKDGLIVPI
FQERLLAVGKWLSINGEAIYASKPWRVQWEKNTTSVWYTSKGSAVYAIFL
HWPENGVLNLESPITTSTTKITMLGIQGDLKWSTDPDKGLFISLPQLPPS
AVPAEFAWTIKLTGVKDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for FUCA1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
FUCA1-DNA (SEQ ID NO: 7)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
CCCATCTGTATTAAAAATACAAAAATTAGCCAGGC
GTGGTGGCGTACCTGTAAACCCAGCTACTCGGGAG
GCTGAGGCAGGAGAATGGCTTGAACCCAGGAGGTG
GAGGTTGCAGTGAGCTGAGATTGCAGCACTGCATT
CCAGCCTGGGCGACAGAGCAAGACTGCATCTCAAA
AGAAAAGAAAAGAAAAAAGAAAAGAAAAGAAAAGA
AAACAGCTGTGATTCAGCAATAGTCATTTTCTCTC
CTTGTCACTGCCAGAGTGAGGAAGTGCTGGGTTCT
GTCAACATAGGCTCTGACTTCTCATGAGGTGCAAG
AAAGAAGCAGCATGAACAAAGGCATAGATTTTGCA
CCTGGAGACACGTATTCTAGTCCCACCTCTGACTC
AAACTAGCTGCATGATCTTGGGCAGCCCCCCAGCC
CTCTCTGGGCTTCAGTTCCCTCCTCGGTACAATGG
GAAGGGTAGGGAAGAGGATGGTGCCTAGGATCTTC
AAAGTCCCAACTCTGATGTGCTGCCATTCTCTCAC
TGGCATGTGGGAACTGAGTGTGCTACGTGGAGTCA
TGAGACTTCTTCTTCCTTTTCTTTTTCTTTTTTTT
TTTTTTTTTTTTTGAGACCGAGTCTCACTCTGTCG
CCCAGGCTGGAGTGCAGTGGTGCGATCTCGGCTCA
CTGTAACCTCCACCTCCCGAGTTCAAGCAATTCTC
CTGCCTCAGCCTCCTGAGTAGCTGGGATTACAGGC
GCACCCCATGCCCGGCTAATTTTTGTATTTTTAGT
AGAGATGGGGTTTCACCATGTTGGCCAGGCTGGTC
TCAAACTCCCGACCTCAGGTGATCTGCCCACCTCG
GCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCA
CCTTGTCTGTTCAGAGACTTCTGACTTCCGTATTT
CCCTCGCTAATGGCCTCACCTCCCGTTTGAGTATG
TGCAGCATGTGCAAATTGCAGAGGAACTGGGGAAC
TTCCCTGCCAGGCAATCCTGGGTCCTCTTGGCTCT
CCACTTCCTCCTTCCTTCCTTCCTTCCTCCTTCCT
TCCTTCCTTCCTTCCTTTCTTTCTTCCTTGGTCTG
GCTCTGTCGCCCAGGGGCTGGAGTGCAGTGGCGGT
ATCTCGGTACAAACTAAGCTATTTGAAATGCCTCG
GAATTCCCAAAGAAAGCTCAGTAAATACCAGACAG
ATGAAACGGTCCTGCCCGCTCTCCCTCTTTCAGTA
CCCAGTTTTCTCTTTCCTCTCCTTTCATAACGTTT
CTTCCCATCATCCCTCTACCTCCTTATTTCTGTCA
GGGCTGTTAGATACCCTTCCGGTCTGTTATCTCCT
CCTCCAGCCTTGTGCTACAGGACAACTCAAAAGCC
CCCTATGGCTCCCAAGTGATCACTAAATAAAACTC
GTGATCTCACTTCAGCCTACCCCTGCAGGATTGCT
GCGGCAAAATGGACTACTCCCAGAGGCGTGATCAC
GGTTCGGTTCACTGCAGCCCAGACTTCCCGGGCTC
AAGCGATCCCGAACCTCCCACCTCAGCCTCTCGAG
TAGCTGGGACTCCAGACGTGCACCACTACGCCAGG
CTCATTTTGTTTATTTTTTATAGAGACAGGCTAGT
CTCCAACTTGTGGGCTCAGAGCGATCCTCCCGCCT
CGACTTCCGAAAGTGTTAGGATTACAGGCGTGAGC
CACTGCGTCCGGCTCAATGGACTCCTTCTTAAATG
TGAGTTCTCCGCACACACTGGGCCTTGCTCACCTC
CACGATTTAACCTCGCAGTTAAGTCCCTTTTCAAG
GTTTTTATTCGTCCTTCAGCGAAGCGCTGTCAACG
CCTCCCTGCGTCTTTCCCTTCTTGAGCACCAGAGG
GCGCTCCTCCGACCCGAGGAGGAAGCGACTCGGGC
CAACCTGTCCAGGTTGTCCCACCCCTTTTTCCTTC
CGGGCCAATCGTTAGTCAGAGTGGGCGGAGCCGCC
CGCGGGCACCTGCGCGTTAAGAGTGGGCCGCGTCG
CTGAGGGG
ATGAGAGCACCCGGCATGCGATCAAGGCCCGCAGG
GCCAGCTCTCCTCCTCCTGCTCCTTTTTTTGGGGG
CTGCAGAATCTGTAAGAAGAGCTCAACCCCCAAGG
AGGTACACTCCTGATTGGCCCTCATTGGACTCACG
CCCACTCCCGGCGTGGTTTGATGAAGCTAAGTTCG
GAGTGTTTATCCATTGGGGTGTATTCAGCGTGCCC
GCGTGGGGGTCTGAGTGGTTTTGGTGGCACTGGCA
AGGAGAGGGCCGCCCGCAATACCAGCGATTCATGA
GGGACAATTATCCTCCAGGCTTCTCATACGCTGAC
TTCGGTCCTCAGTTTACAGCTAGATTCTTCCATCC
AGAGGAGTGGGCCGATCTTTTCCAGGCGGCTGGAG
CTAAGTACGTCGTTCTGACGACAAAGCACCATGAA
GGGTTCACCAACTGGCCAAGTCCAGTGTCCTGGAA
CTGGAACAGTAAGGATGTCGGTCCTCATCGGGATC
TGGTAGGCGAACTTGGGACTGCTCTCCGGAAGCGC
AATATACGCTATGGTCTTTATCACAGTCTGCTGGA
ATGGTTCCACCCACTGTACTTGCTGGACAAGAAGA
ACGGATTTAAAACCCAACATTTTGTTAGCGCAAAG
CATATGCCAGAGTTGTACGACCTGGTAAATTCCTA
TAAACCCGACCTCATCTGGAGCGACGGAGAATGGG
AGTGCCCGGATACTTATTGGAACTCAACTAACTTT
CTCTCCTGGCTGTATAATGACTCCCCTGTGAAGGA
CGAAGTTGTTGTAAATGACAGATGGGGTCAAAACT
GCTCATGTCATCACGGGGGATACTATAATTGCGAA
GACAAGTTTAAGCCTCAATCTCTTCCCGATCATAA
ATGGGAGATGTGTACTTCTATTGACAAGTTTAGTT
GGGGATACAGGCGCGACATGGCCTTGTCTGATGTT
ACGGAGGAATCAGAAATCATCTCCGAGCTGGTACA
AACGGTGTCATTGGGAGGCAACTACCTGCTGAACA
TAGGCCCAACGAAAGACGGGCTTATCGTGCCGATT
TTTCAAGAACGCCTTCTCGCAGTTGGCAAATGGCT
CTCTATTAATGGGGAAGCTATTTACGCGTCAAAAC
CTTGGAGGGTCCAATGGGAGAAAAACACCACTAGT
GTATGGTACACAAGCAAAGGAAGCGCCGTCTACGC
TATCTTCCTGCACTGGCCAGAGAATGGCGTACTCA
ATTTGGAATCACCTATAACCACATCCACGACTAAG
ATCACCATGCTCGGGATTCAAGGTGACCTTAAATG
GTCTACAGACCCAGATAAAGGTCTTTTTATTAGTC
TTCCCCAGCTGCCTCCCAGCGCGGTTCCGGCCGAG
TTCGCCTGGACGATCAAGCTGACCGGGGTTAAAGA
CTATAAAGACGATGATGATAAATA
The GALC protein sequence is:
(SEQ ID NO: 8)
MAEWLLSASWQRRAKAMTAAAGSAGRAAVPLLLCALLAPGGAYVLDDSDG
LGREFDGIGAVSGGGATSRLLVNYPEPYRSQILDYLFKPNFGASLHILKV
EIGGDGQTTDGTEPSHMHYALDENYFRGYEWWLMKEAKKRNPNITLIGLP
WSFPGWLGKGFDWPYVNLQLTAYYVVTWIVGAKRYHDLDIDYIGIWNERS
YNANYIKILRKMLNYQGLQRVKIIASDNLWESISASMLLDAELFKVVDVI
GAHYPGTHSAKDAKLTGKKLWSSEDFSTLNSDMGAGCWGRILNQNYINGY
MTSTIAWNLVASYYEQLPYGRCGLMTAQEPWSGHYVVESPVWVSAHTTQF
TQPGWYYLKTVGHLEKGGSYVALTDGLGNLTIIIETMSHKHSKCIRPFLP
YFNVSQQFATFVLKGSFSEIPELQVWYTKLGKTSERFLFKQLDSLWLLDS
DGSFTLSLHEDELFTLTTLTTGRKGSYPLPPKSQPFPSTYKDDFNVDYPF
FSEAPNFADQTGVFEYFTNIEDPGEHHFTLRQVLNQRPITWAADASNTIS
IIGDYNWTNLTIKCDVYIETPDTGGVFIAGRVNKGGILIRSARGIFFWIF
ANGSYRVTGDLAGWIIYALGRVEVTAKKWYTLTLTIKGHFTSGMLNDKSL
WTDIPVNFPKNGWAAIGTHSFEFAQFDNFLVEATRDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GALC and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
GALC-DNA (SEQ ID NO: 9)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTCCTCTGTCATCACCTTGGTATTTCCCATC
TAGTCACGGTATTAAGTGGGTCTTATGCGCTTGTTAAGAGCTGGTAAGAGAAGCTTAACATTCACTTG
ATGGAATGGTTACTGTGGCTTGTATCCACAGGAGCTCCAGCTCATGCTTAAAATACTGTGTTAGAACA
AATGGATCAGAGTGAATTCTGTAACAGTAAATCCACAGAACTGAAAATTACTGACTTGCATCATAAAC
TGGTTGCAGTGGCAAGGCAGAGAGTTCAGATTCGTGTTGTACTGGGGAAAGAAGAAACCAAAGAAAAT
AAGTGGTTCATACACAGGGGACTATTTAACTGATCCAAGCCAGAAGACTACTGAGGGTGAAAGGAGCA
TTATCAGTAATTATGTTTAGACAAAAGTTGTGACTGTCCTTAGTAAACCAGGATAGACGTAGAGTCAA
TTCAAAAAGAAAGAAAGAACAAACATATCTAATGTACATTAAGAACCCAGGGATATCGGGTTCTTAAT
GTGCATATTTATTGGATTGCCCAGAGCTTTGACCTTCAAGTATAATTGAGTTCTTGAAACTTAGATTT
AGGTTTGTGGTTAAGGGGCAAAATAATCAGATTCCAAATAGGGTTCTGCAGACAAATCCCACAGGTCC
TAAAGTCTCTGGGTCTTTTCCTTGCCATTGTGGTATCTCAGGGGCTTGTGTAGGCAATGATAACCAGT
TCCATACTTCTGCTAAGAGAAATTTGGGGATCAGAAAATCTTTCTCTGCAGCTCTTCAGAGTCTCTTT
AATTTACTTCAATAACAAGGAAATCAGAAATCTCAGGACAGTGCTGGATGTGGCAGAAATTCAGGGCA
ATTCACAACTTTCCTACCAATTTAGAGTTACCTGTCTGGAATCACTTCAACTGACAGTGGAAGATAGT
TTATAAAATTGTAGGGGAGGCAAAATTTCACCTTCGTCCCTGTAGGGTCCCAGCATGGCCCTAGTATT
AAATTGATTTAAGATATTAATAGACTGACAGGAGACAACCACACAAATGTTTATTTTACATAGCACGG
GGGCCCTCATTAAAAAAAAAAAAGACCTAAAGCAGCAGTTAAGAGCCAATTGCTTATAGAGTGAAATG
GACAAAAAATAGTAGTTGTGAAACATGATAAGGCGAAGGGGCTTGGGGTAAAGAAGCGACTAGAAAGA
TAGGGATTAACAAATTTTGTTTGGACAGATTTCCCTCGACTTCAACTTTCTGTCCTTGAAGATAACAA
TGTTATTTTATAGGGAAGACATCTTTCACATGGGAATTTCATCTCCTCCTTTTAAGACACATAATATC
CATGACAGTGATCTTGCACCTGCTGTTTTTAAGTGCCTTTAATTTAAAATAGTCAATATGCCACAGCA
GCATATTTTGAGGTGGTATATTATTAACTCCTTCAAGGCTAAAAGCTTTGAATATGCCGGGGTAGTTA
CCAGACTGGAGAACCTTCTCAGCTATTTGCCACTTGTGGAATGCATTCAAATGTACTGAGTGCTTATT
AACTTTTCTCTCAGTCCCTCACTCTGCTGCTCTTCTCGCCTCATCTCACATAAGGGAAAACTCAGGCT
CCAAAAGCAAAGTGATTCCACCAAGATGACAATGGAATCGGGACCTGGTGTCCAAGCCTGGTCCTCGC
ACGAGGTAGATACTCCCTGAGATGCTGGGGAAGAGCCATGGTAGGGCCACTCATGGCCCTCTTCCTTT
GGCGGACCTTGGAATCCACCTTCCCTGCGTTAAAGTGCTCCACCAGGTGACGCCGGAAGAGAAGCCAG
CAGTAAGTACATGTGAAATCCAGTAGCTGACCACAGACACGCGAGCGATAAGAAAAAGCTCGCTGCTT
CTTTTCTCAACACTCCGCCAGCTGCGTCAGAGGCCCTTGACCCGCACTCAAAATGGCGGCGGCGGCGT
CAGCATCAGCGGCCTCCTGCCCGTATCTATCGTGGCGGCGACGGGACCCGCCTCCCTGGGCGCCGG
ATGGCCGAATGGCTCCTTTCAGGATCATGGCAGCGCCGA
GCTAAAGCGATGACGGCTGCCGCGGGCTCTGCTGGGAGAGCAGCTGTTCCTCTTCTGCTTTGTGCCTT
GTTGGCACCTGGCGGAGCCTACGTTTTGGATGACTCTGATGGATTGGGTCGCGAGTTCGATGGTATCG
GTGCTGTGTCTGGTGGCGGAGCCACGTCCAGGCTGCTGGTAAATTACCCGGAACCATATCGAAGCCAA
ATCCTTGACTATCTTTTCAAACCTAACTTTGGAGCGAGCCTTCATATTCTCAAGGTCGAAATAGGCGG
AGACGGGCAGACAACTGATGGCACCGAGCCGTCTCATATGCATTACGCTTTGGACGAAAATTACTTTA
GAGGATACGAATGGTGGCTGATGAAGGAAGCCAAGAAAAGAAATCCCAATATTACCTTGATCGGCTTG
CCGTGGTCATTTCCCGGGTGGCTGGGCAAGGGATTTGATTGGCCGTATGTAAATCTTCAATTGACGGC
CTATTACGTAGTTACATGGATAGTAGGTGCCAAACGCTACCATGACCTGGATATTGATTACATTGGAA
TTTGGAACGAACGATCCTATAACGCAAATTACATCAAAATTCTCCGAAAGATGCTCAACTATCAAGGC
CTCCAGAGAGTTAAAATCATCGCGTCAGATAACCTTTGGGAGTCTATTTCTGCCTCAATGCTGCTCGA
CGCGGAACTTTTTAAGGTGGTTGACGTTATAGGGGCGCATTATCCAGGTACCCACAGCGCTAAAGACG
CAAAGCTCACGGGCAAAAAGCTGTGGAGCAGTGAGGACTTTAGTACCTTGAATAGTGACATGGGTGCA
GGGTGTTGGGGTAGGATACTGAACCAGAATTACATCAATGGATATATGACGAGCACTATAGCATGGAA
CTTGGTAGCGAGTTATTACGAGCAGTTGCCGTACGGTCGATGTGGTCTTATGACGGCGCAAGAACCGT
GGAGCGGGCACTATGTGGTCGAGAGTCCCGTTTGGGTAAGCGCTCATACAACTCAATTCACGCAGCCT
GGGTGGTATTATCTCAAGACCGTTGGACACCTTGAGAAAGGCGGGAGTTACGTAGCACTTACCGACGG
CTTGGGGAACTTGACTATTATCATTGAAACAATGAGTCACAAACACAGCAAATGTATTAGGCCTTTCC
TGCCATATTTTAATGTCTCTCAGCAGTTCGCTACTTTTGTGCTTAAAGGAAGCTTCAGTGAAATACCC
GAGCTCCAAGTGTGGTATACCAAACTTGGTAAAACTAGTGAACGATTTCTTTTCAAACAACTCGACTC
ACTTTGGCTGCTTGACTCTGACGGAAGCTTCACTCTCTCTCTTCACGAAGACGAGTTGTTTACTCTCA
CTACGCTTACTACTGGACGCAAGGGTTCATATCCTCTTCCTCCAAAATCTCAGCCATTCCCTTCCACA
TATAAGGATGATTTTAACGTCGATTATCCCTTCTTCTCCGAAGCGCCGAATTTTGCGGACCAAACAGG
TGTATTTGAATATTTTACTAACATTGAGGACCCAGGAGAGCATCACTTCACCTTGCGACAGGTCTTGA
ACCAGAGACCAATCACTTGGGCAGCCGACGCCTCTAATACCATATCAATTATCGGTGATTACAACTGG
ACTAATCTCACAATTAAATGTGATGTCTATATTGAAACTCCTGACACTGGAGGTGTTTTCATCGCCGG
GCGCGTCAACAAAGGAGGTATCCTTATCCGATCAGCTCGCGGTATCTTTTTTTGGATTTTTGCGAATG
GAAGCTACCGAGTTACAGGTGATCTTGCTGGGTGGATTATCTACGCCCTCGGCAGAGTAGAGGTTACT
GCCAAAAAATGGTATACTTTGACGCTGACGATCAAGGGCCACTTCACAAGTGGTATGCTTAACGATAA
AAGCCTGTGGACGGACATTCCAGTGAACTTTCCTAAGAACGGTTGGGCCGCCATTGGGACACACTCAT
TCGAATTTGCCCAATTCGATAATTTTCTCGTGGAGGCAACCAGAGATTACAAGGATGATGATGACAAA
TA
The MCOLN1 protein sequence is:
(SEQ ID NO: 10)
MTAPAGPRGSETERLLTPNPGYGTQAGPSPAPPT
PPEEEDLRRRLKYFFMSPCDKFRAKGRKPCKLML
QVVKILVVTVQLILFGLSNQLAVTFREENTIAFR
HLFLLGYSDGADDTFAAYTREQLYQAIFHAVDQY
LALPDVSLGRYAYVRGGGDPWTNGSGLALCQRYY
HRGHVDPANDTFDIDPMVVTDCIQVDPPERPPPP
PSDDLTLLESSSSYKNLTLKFHKLVNVTIHFRLK
TINLQSLINNEIPDCYTFSVLITFDNKAHSGRIP
ISLETQAHIQECKHPSVFQHGDNSFRLLFDVVVI
LTCSLSFLLCARSLLRGFLLQNEFVGFMWRQRGR
VISLWERLEFVNGWYILLVTSDVLTISGTIMKIG
IEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFF
HNYNILIATLRVALPSVMRFCCCVAVIYLGYCFC
GWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVT
FAAMQAQQGRSSLVWLFSQLYLYSFISLFIYMVL
SLFIALITGAYDTIKHPGGAGAEESELQAYIAQC
ODSPTSGKFRRGSGSACSLLCCCGRDPSEEHSLL
VNDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MCOLN1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
MCOLN1-DNA (SEQ ID NO: 11)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGACCCTGACCCTGGCTCTGGGCCGGGCACTC
TGCCGGATCCCAGCTCCAAACCCCTCCCCGGCTCCAGATCCACCCCCAGCCCTACTCCTGTGGAATCT
TCTGACCCAAAGGCTGGGCACGACGCTGGTCCCGACCTTGTGCCCAGCCCAGACCTTGATCCTGTGCC
CAGCCCAGACCCTGATCCTGTGCCCAGCCCTGATCCCAACCCTGTGTCCTGCCCTGACCCCTGTTCTC
CCACTCGTGGCACTGTCAGCCCAGCCCTCCCTACCGGCGAGAGTCCAGAGTGGGTACAGGAGCAAGGG
GCACTGCTGGGGCCTGATGGCTGAAGGAGACGCCGGCATCCTCGGGGGCCTGGGGAAGTTGTGTGTTG
TGCAGTCAGTAAAATCCTCCCACTGCCTCCGGGCTCTGTGTCGTGGCTTGCCTTTTGTGCTTTCTTTC
TGAGCACAGCCCCTTGCTCCGGAGATGGGACATTGTGGCCAGGGCCAGCCACAATCTGGAGCTCCAGT
GTCCTGGCTTCCTTCTTGGGCCCACCAGCTAGACTTTCCAGCTTAACCCACAGTGTCTCATCCTGGTC
CATCCCACTAGTCACCACTCTCTGTTCCTCTCACTTACCCCTTGCTCTTCAAAGCCCATACAGTAGGT
ATACAAGTGGACAAAAAAAGTTGCTCATTTATGCAATCAACAAACATCTCTGGATTGCTGGGGTCTCA
GCAGGGAACAAGATAAATATGGCCTCGACCTGCATGGAGCTCATAGATACTAAATTCAGAATACTTAA
AAAATAATTACGGGGTATAGTACATTCTAGGAGAAGCATAACAAGACTTCTGATATAAATGGCAGGCA
GCTTTCTCAATGAAGGATTTTGTAATCCCAATAATCACTAATTTAATAATCAGTACTGTTTGCCCAGC
CTTATGCGATAGTTTTTGCATTCTCTCATTTAATCCTCTCAACAGCCCCAGTAGGTAGATGACTTTGA
ATATCCCCATTTTGCAAATGAGAAAATTGAGGCACATTTTTTTTTTTTTTTTTAGACAGTCTTGCTCT
GTTGCCCAGGCTGGAGTGCAGTGGTGTGATCATAGCTCACTGCAGCCTCGACCTCCTGGGCTCAAGCG
ATCCTCCCACCTTAGCCTCCCGAGTAGCTGGGATTGCCGGTGCATGCCACCGCCCACTGCGCTCAGCT
TGGAGTTGAAGGGACTCTGGAAGATGTAGAAGTGGCATTGTCAGTGCCTAGATTTAAATCCCAATTGC
CCTCCAGGGTCCAAATTCTTAACCATTACGCTCCAGGGCAAAAGTATGCAAAGGCTCTGGGGCTATAG
AAAGATGAGCTTTGGATGGAGGTAGGAGCCAGATCAGAGGGCCCTGATAGACGAGAGTGGGGACTCTG
CCTGTCATTACAGAGCAATGGGAAGCCGAGGGCAGGTTCTCGCAGGAAGGATAGGAATTATTCTTTGA
AGATGCTTGTGGCTGCTGGGTAGAGAGTGGAGTGGAGGGAGGCTGAGATCGGGGAGGAGGTTGCTGCA
AAGATCCAGGCCAGGAATGTTGGAAGACTCTGGGCTGGGGGCCATGGGGTGGGGATAAGTGGTTCTAT
TTGATACATAATTAGGAAATCGTGTTTGCTGAAGATGCGCAGGAGAAGGGTAAAAGGAGTTTCTGGGA
GAAAGAGGAAGACAGCGTTGAGATAGTAGGCAGGGTCATCACCAGGCACCAAGGAGGATAAGGGGTCA
AGCTCTGGACATGGAAGTCACAAGCCTGGCACCGGATTCGGGGCATGGCCGGGAGCCAGGGCAGAGCT
CGTCGTTGCCAAACTCAGAGTCAGCCCATCCCCCGCCACCCAGAGCGCGTCGGCGCTAGGACCTAGCG
ACTGCCTTCGACCCAGAGGGCGCCGGCAGAGGCACGCATGCGCGCTGTTCCGGCAGGGGTTGTCGTGG
CGCAGGGGGCGGGACCAGAGGCGGTCACGTGAGGGGCTCTGGGCTACCGGGTCACGTGACCGAGGC
ATGACTGCGCCGGCAGGTCCACGAGGGTCTGAAACAGAA
CGGCTCCTTACTCCCAATCCCGGCTATGGGACACAGGCCGGTCCTAGCCCTGCCCCACCCACACCCCC
TGAGGAGGAAGATCTGAGGAGACGGCTCAAGTATTTCTTCATGAGCCCGTGCGATAAATTTCGAGCTA
AGGGACGAAAGCCGTGCAAGCTGATGCTCCAGGTGGTAAAGATTCTCGTAGTTACTGTGCAACTCATC
CTTTTCGGTCTGTCCAATCAGTTGGCAGTCACTTTCAGAGAAGAAAACACTATCGCTTTTCGGCATCT
GTTCCTGCTGGGTTATAGTGACGGTGCAGATGACACCTTCGCCGCCTACACTCGCGAACAACTTTACC
AGGCTATTTTCCACGCGGTAGATCAATATCTTGCGCTCCCCGACGTTTCATTGGGGCGGTACGCCTAT
GTTCGCGGAGGAGGCGATCCCTGGACCAACGGCAGTGGTCTCGCATTGTGCCAACGATACTACCACCG
GGGGCACGTAGATCCCGCCAACGACACCTTCGACATAGACCCGATGGTAGTAACAGACTGTATTCAGG
TGGACCCCCCCGAGAGGCCACCTCCACCACCTTCCGATGACCTGACGCTGCTCGAGAGCAGCAGTTCT
TATAAGAATCTTACCCTTAAATTCCATAAATTGGTAAATGTAACCATCCATTTTCGCCTCAAAACTAT
CAACCTGCAAAGCCTCATAAATAACGAAATTCCGGATTGTTACACTTTCTCTGTTTTGATAACATTCG
ACAATAAGGCCCACAGCGGAAGGATTCCGATATCCCTTGAAACACAAGCACACATACAAGAATGCAAA
CACCCTAGTGTCTTCCAGCATGGCGATAATAGTTTTAGACTGCTGTTCGATGTAGTTGTGATCCTTAC
ATGCTCACTGTCATTCCTCCTTTGTGCACGATCACTTCTTCGGGGTTTCCTGTTGCAAAATGAGTTTG
TGGGATTTATGTGGAGGCAACGAGGACGCGTCATATCTTTGTGGGAACGGCTTGAGTTCGTCAATGGA
TGGTACATACTTTTGGTTACATCCGATGTGTTGACTATATCCGGTACAATTATGAAAATTGGCATTGA
AGCGAAGAACCTCGCCAGTTATGACGTTTGCAGTATCCTTCTGGGAACGTCCACCCTCCTCGTATGGG
TAGGAGTCATACGGTACCTGACTTTCTTCCATAACTATAATATACTGATCGCAACCCTTCGAGTCGCG
CTTCCGAGCGTGATGAGGTTCTGTTGCTGCGTAGCTGTTATCTACCTGGGATACTGTTTCTGTGGATG
GATCGTACTCGGCCCGTATCACGTAAAGTTCCGGTCCCTTTCTATGGTCTCCGAATGTCTTTTCAGTC
TCATCAACGGTGACGATATGTTCGTCACCTTTGCTGCGATGCAAGCTCAACAAGGGAGGAGTAGTCTG
GTTTGGCTTTTTAGTCAACTGTACTTGTACTCCTTTATCAGTCTTTTTATTTACATGGTGCTCTCATT
GTTCATCGCACTTATCACGGGCGCCTACGACACGATTAAACATCCGGGTGGAGCCGGCGCCGAGGAAA
GTGAGCTCCAAGCCTACATAGCGCAATGTCAAGATTCCCCGACCTCAGGCAAGTTCAGGAGAGGCTCC
GGAAGCGCCTGTTCTTTGCTTTGCTGTTGCGGGAGAGACCCATCCGAAGAGCACTCCTTGCTGGTCAA
TGACTATAAAGATGACGACGATAAATA
The PPT1 protein sequence is:
(SEQ ID NO: 12)
MASPGCLWLLAVALLPWTCASRALQHLDPPAPLP
LVIWHGMGDSCCNPLSMGAIKKMVEKKIPGIYVL
SLEIGKTLMEDVENSFFLNVNSQVTTVCQALAKD
PKLQQGYNAMGFSQGGQFLRAVAQRCPSPPMINL
ISVGGQHQGVFGLPRCPGESSHICDFIRKTLNAG
AYSKVVQERLVQAEYWHDPIKEDVYRNHSIFLAD
INQERGINESYKKNLMALKKFVMVKFLNDSIVDP
VDSEWFGFYRSGQAKETIPLQETSLYTQDRLGLK
EMDNAGQLVFLATEGDHLOLSEEWFYAHIIPFLG
DYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PPT1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
PPT1-DNA (SEQ ID NO: 13)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTGGTCTGGCACAATGGCTCACAGCTGTGAT
CCTAGAACTTTGGGAGGCTGAGGGGGGCGGATTGCCTGAGCTCAGGAGTTCGAGACCAGCCTGGGCAA
CATGGCGAAACCCTGTCTCTACAAAAAACACAAAAAATTAGCGGGGCATGTTGGTGGTGTGTCTGTAA
TCCCAGCTACTCGGGAGGCAGAGGCACGAGAATCGCTTGAACCCGGGAGGTGGAGGTTACAGTGAGCC
AAGATCACGCCACTGCACTCCAGTCTGGGGGACAGAACAAGACCCTGTCTCAAAAAAAAAAAAAAATT
GCATTCAGATTGCTTCACAAGTGTCTTTCAGTTATTGCTCCAGTTTAAAGAAACCTTTAAAGAAATTA
TAAATAGTTCATTAAAGGCAGGAAACTTCATTGAGCGGGCTATATTCACAGAAAAATCCTGAAACTAC
TTCAATTTGTAAGTCTTAAGTTAAAATAAAATGCTTATACAATAAGCTTATTTTTCTTAAAACAAAAC
TGTATACTGTACTGTATAATGCTTTATGATTCTGCATTTTTTTTTCTTTGAGACAGAGTTTCACTCTT
GTTGCCCAGGCTGGAGTGCAGTAGCTCAATCTTGGCTCACTGCACCCTCTGCCTCCTGGGTTCAAGTG
ATTCTCCTGTCTCAGCCTCCTGAGTAGCTGGGATTACAGGCACCCACCACCATGCCCGGCTAATTTTT
TGTATTTTTAGTAGAGATGGGGTTTCATCATGTTGGCCAGGCTGGTCTCAAACTCCCAACCTCAGGTG
ATCCACCTGCCTCAGCCTCCCAAAGTGCGCCCAGTGGATTCTGCATTTTAATCGACTTTTCAACTAAC
AACTTACCTCTAGTCCCAATGGCATGGAATAGAAGAGATTACAGACCGTGGGTTTGTAATCGACTTTT
CTTTTACAACATATTAAGGGCATTTTTCATGTCACTTTATGTAAATTTACCTCATTTTTCTTTTTTGA
GAGAGACAGGGTCTCACTGTTGCCCAGGGCAACAGCGAGATCATAGCTCAGTGCAATGGCGAGATCAT
AGCTCAATGCAGCCTTGAACTCCTGGGCTCAAGTGATCCTCCCACCTTAGCCTCCCCAGTAGCTAGGA
TTACAGGCACATACCACCACCCCTGGCTAATTAAAAAAAAATTTTTTTTTTGTAGAGATGGGGTCTTG
CTATGCTGCCTGGGCTGTACTCTCTTTTTATTTATTTTTTATTCTTATTTTTTGAGACAGAGTTTTGC
TCTTGTTGCCCAGGCTGGAGTACAATGGTATGATCTCAGCTTACCGCAACCTCTGCCTCCCGGGTTCA
AGAGATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGATTACAAGTATGCGCCACCACACCCGGCTAAT
TTTGTAATTTTAGTAGAGACGGGATTTCTCCATGTTGGTCAGGCTGGTCTCGAACTCGCTACCTTAGA
TGATCTGCCCACCTCAGCCTCCCAAAGTGCTGGGATTACAGGAGTGAGCCACCGCGCCCGGCCCTATA
CTCATTTTTTATAAAACTGGCCTCATATTATTCCATTGTATAGTGGATACACTCTAATTTCTTTATAA
ATTATTTAAACTATTTTTTGATGTTTTGTTGAAAAAAAACTTGAGCAGGGAACTGATATTATGAAGGT
GGATTGAGGGATGAATGTGGCAATAGAGCATAAAATGAATTAAAGAGGAGAGAATGGAAAAGGAAATG
GTTGATGAGAGACCCTTGAAATAATCCAGCTGAGATTAGGCCAGTTAGTGGCCATGGGTTTCCCCCTC
ACTCTTATGCATCCAACATATGCTTTCGTCCGTCTTGAAGTCCCGACATTTCTAGAAAACACAGTTGT
CTTTCTCCTCTCTACCTTAGCTCATCTCAGTCCTTCTGAATTTCATCTTTGCTTGTTGAAATCCTACC
TCTCCTTCAATATCCAGAACAAACCCCACACCCTGCCATGATTGGTCCTGGCTGGAAACCGTCCCTCC
TTCTTTCTTCCTTCCTCTGTGCATGTTTCTTGCAAAGGCAGTACAGGGCAGTGGTGAAGAGCAACGAC
TTTGGAACCACCAATTTGCTATCTCTGTGACCTTGGGCACCTTACTCAGTGCCAATTCGCAGTGCCTC
AGTGTCCTCACCTGTCAGGGGGAGAAGTGCATACAGCATTGTTATGAAGAGTGAATTAGTTAAAGGTT
GTAAGAATAGTGCCTGATAGCATCTGATCAGCACTGAATATATGTTAGCAATTATTTTGATTCACCGC
AGAGGGCGGTCTACGAGAGCGCAGAGCCCCACTCGGCCAGCGGGGTCTGGCGGGGGACCTGTCGCGCT
GAAAGCTCCAGGGTAGGGCCGACGCCCATCAGGCTGGGCATCCGTTCGGGATGCGCAGGTTGCGATCT
GCAACCGGCGGCGCCACGCCCAGGCGGGCGGAGCGCGGTTCCCGGAGTCTCGCGCCCGCGGTCA
ATGGCGTCTCCTGGTTGTCTTTGGTTGCTTGCCGTCGCGTT
GTTGCCTTGGACATGTGCTTCTCGGGCTTTGCAGCACCTCGATCCCCCAGCCCCATTGCCTCTTGTAA
TCTGGCATGGCATGGGTGATTCATGCTGTAATCCCCTCAGCATGGGGGCCATAAAGAAAATGGTAGAG
AAAAAGATCCCAGGCATATACGTACTCTCACTTGAGATAGGGAAGACCTTGATGGAAGACGTTGAGAA
CTCTTTTTTTCTCAATGTTAACTCCCAAGTCACTACGGTATGCCAGGCGCTGGCGAAAGATCCTAAAC
TTCAACAGGGGTATAACGCCATGGGATTCTCTCAAGGTGGGCAGTTCCTTAGAGCGGTCGCCCAGAGG
TGTCCATCCCCCCCAATGATTAATTTGATCAGTGTGGGTGGACAACATCAAGGCGTGTTTGGCCTCCC
CAGATGTCCAGGTGAGTCATCTCATATCTGTGATTTCATCCGGAAGACATTGAACGCAGGTGCGTATT
CAAAGGTAGTGCAGGAGAGGCTGGTGCAGGCTGAGTACTGGCACGACCCTATCAAGGAGGATGTCTAC
CGAAATCACTCAATTTTCCTTGCAGACATCAACCAGGAGCGAGGCATTAATGAAAGCTATAAAAAGAA
TTTGATGGCTTTGAAAAAATTTGTTATGGTCAAGTTCCTCAATGACTCAATAGTCGATCCGGTGGATT
CCGAGTGGTTCGGGTTTTATCGGTCAGGTCAAGCGAAAGAAACAATTCCCCTTCAAGAAACGTCACTT
TATACGCAGGACCGACTCGGCCTGAAGGAAATGGATAACGCTGGGCAACTGGTATTTTTGGCTACCGA
GGGCGATCACCTGCAGTTGAGCGAGGAATGGTTCTACGCTCACATCATACCCTTTCTTGGGGACTACA
AGGACGACGATGACAAGTA
The SMPD1 protein sequence is:
(SEQ ID NO: 14)
MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMG
LVLALALALALALALSDSRVLWAPAEAHPLSPQG
HPARLHRIVPRLRDVFGWGNLTCPICKGLFTAIN
LGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSI
VHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHW
DIFSSWNISLPTVPKPPPKPPSPPAPGAPVSRIL
FLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPA
SRPGAGYWGEYSKCDLPLRTLESLLSGLGPAGPF
DMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVR
KFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSS
RWLYEAMAKAWEPWLPAEALRTLRIGGFYALSPY
PGLRLISLNMNFCSRENFWLLINSTDPAGQLQWL
VGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYY
RIVARYENTLAAQFFGHTHVDEFEVFYDEETLSR
PLAVAFLAPSATTYIGLNPGYRVYQIDGNYSGSS
HVVLDHETYILNLTQANIPGAIPHWQLLYRARET
YGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHK
GHPPSEPCGTPCRLATLCAQLSARADSPALCRHL
MPDGSLPEAQSLWPRPLFCDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SMPD1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
SMPD1-DNA (SEQ ID NO: 15)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGAGCACTTACTAGCTAGCTGTGGGATCTTGA
GCCACTTACTTAATCCTACTTTCCTTCTCCGTAAAATGGGGATAATTATAATACCGACTTCCAAATTT
GTTGTGAGGATTAACGTAAGGCAGAGTCCTCAGAAAAGTACCTACAGAGGGTTATTCGGGCCAAGGGC
CAAGGTTGAGGACTGCGACCCAGGACACACTTGCAAGTTGTCTTGGGGGAGCACTCTGGACAACAAAA
GAGAGGCTCATATTTTCAAAGAAAAAAAGATGAATTAGGAGAGGAAATGAATACAAAAGTTGTTCATC
AGGAATTCTCATTGTTTACAGAAATAACACTGGTTATACATTGTTTAGCGCTTGGCTATACATTGTTG
AACTATAAGGTGTATGGCATTTAATGGCTACTTGGCATAGCAAGTGGTTTCAAGAGATAATTACTTAG
CTCAAAGAAGAGTGAGAGTGACTGTTGCTACATTTTAAATGCCTGTCTGGGCCTGATAATTTAAAGGG
GCTCATCTTCCTTAGATAAAAAGGTTTTGTTTTGTTTTGTTTTTCATAGTACATAATCTTAAAAATGC
ATGCTAATTATTACTGTGAGTACTCTATCTGAGATGATGTCCCCAGAACTGGGGGGAAAAAACACTTG
TAAAAAATTATCAAAGGAAAGAACTGACAGGACTTGATAGCTCTGAGGATTCCTCAGAAGCACTCGTC
AAACAGCTTAGGGTTTAATTGCTATTCTGCCACTTAACTTCTTTGTGCCTCATCCTATCTGTAAAGGA
GGGTAATAATAGTATTTGCAGGGACCAAGGGAAACTTTCCCTTCGCCCTCTGAAATTCTGCTGAAAAA
TCAACCCACAAAAAACAGATTAATTGAAGAAAAGGCATAGAAATTGTATTAATGTGTCCACGGGGAAC
CACAGAGTGACTACCCACTTCCCAGACGAGTTCAGAAGCTTAGGTGTCATTCAGGCAAAGGGGGTTGT
GGGAGTGAGGGGAAGAGGAATTCTGCTGAGGGAGAAGGAATGGATCAGGGAACAGATTAACTAGCACA
TTATCATGTGAAGGGGTCTGTTCAGGTGTGATTATATTCTTGGTTTTGTAGGGAGGGGAAGAAAAAAA
CCGTTGTTCCTTTTGATGGGTCTGGACGCTAGGTAACGGCTTTGGGAGAGAGGGCGCGGGAGTAGGAA
GGCCAGACACACCTTAAGGCTTAACTTAGTAAGTCAAACCACCATATTTTGGGTATGGATTTCTGAGC
CCCAATATAATAGGTACTTCTTAGGGTTGTTGTGAGAATTGAAGATTATTAATTATAAAGTGCCTGGG
TTGGTGCTTGGCACATCATAAACAACTCCATAAATGCTCGCTTTTACTGTCGTGGATACACGGAGGTG
GGAGACCCAATTGGGTTCCCGCCCATGTTATTGGCCCCCACGGCTATATGGTCTTTACGGCTTCCTAG
TCTCTTCACCATCTCTAAGGTTTGTTTCCTCATCTGAATCACAGGTGAGTGATTCTCAGGGTGACTCA
AGAGGGCTGGTGCCAGTGGCAGAGCATGGGGAATCGAGGGAAGGCGCCTTCCTGTCAGAGGCAACACA
CCCAGTGGGAGGATCCTGCCCGCCCTGCTCTCTCCTACCTCCCCTTCCCGGGCTAAACGCTGGGGTCG
GTCTGGCAGCTATTCCGGGAATCTGAGCGCGGATTCTGACAAAGGAGACGTCTTCCACCGACCACATC
ACATGGAGCTCCAAAGCACGAGCACGGCCTCCCGCGGCTGTGACCTCAAGGCGGAGCCCCTGGTGACC
TCAGGGAGAGTCCCCACCCCCGCAGCCCGTGCGCCCGGGGCAGGGCGGGGGCAGGGAGAGGGGGCGGA
ATCGGGGCGGTCCCGGGAGCGCCCCGCCCCCTCCGCCTCCGCAGCGTTGACAGCCGCCCGCCACCGAG
AGATCAGCTGTCAGAGATCAGAGGAAGAGGAAGGGGCGGAGCTGCTTTGCGGCCGGCCGCGGAG
ATGCCAAGGTATGGTGCTAGCTTGAGGCAATCCTGTCCTCG
CTCTGGCAGGGAACAGGGACAGGATGGTACGGCGGGAGCCCCGGGCCTGCTGTGGATGGGGCTCGTGC
TTGCATTGGCGCTCGCCCTTGCTCTGGCGTTGGCACTGTCTGACAGTAGAGTCCTTTGGGCGCCTGCA
GAAGCCCACCCACTGTCTCCCCAAGGGCACCCCGCCCGACTCCATCGAATCGTACCTCGCCTGCGGGA
TGTTTTCGGTTGGGGCAATTTGACCTGCCCAATATGTAAAGGCCTCTTTACGGCCATCAACCTCGGTC
TCAAAAAAGAACCTAATGTCGCTCGCGTTGGCTCAGTTGCCATCAAGCTGTGTAATCTGTTGAAAATA
GCTCCGCCGGCAGTGTGTCAAAGTATTGTGCATCTGTTCGAGGACGATATGGTTGAGGTATGGCGACG
ATCCGTCTTGTCCCCCTCTGAGGCCTGCGGGTTGCTGTTGGGGTCTACATGTGGCCATTGGGACATAT
TTAGTAGTTGGAACATCTCATTGCCGACGGTCCCGAAGCCCCCTCCTAAACCTCCTAGCCCGCCAGCG
CCTGGTGCCCCTGTGTCTCGGATTCTCTTTTTGACAGATCTCCACTGGGATCATGATTATTTGGAAGG
GACCGACCCCGACTGTGCTGATCCTCTTTGCTGCCGCCGCGGTAGTGGACTTCCTCCTGCCTCTCGAC
CAGGGGCGGGCTACTGGGGGGAGTATAGCAAGTGCGACCTTCCCCTCCGAACCCTCGAGTCACTGTTG
TCAGGGCTCGGCCCCGCAGGACCTTTTGACATGGTTTACTGGACAGGAGACATACCAGCACACGACGT
TTGGCATCAGACTCGGCAGGATCAGCTGCGGGCGCTCACTACTGTTACAGCGTTGGTTCGCAAGTTTC
TGGGTCCCGTCCCAGTGTACCCCGCTGTTGGAAACCACGAGAGTACGCCGGTGAACAGTTTCCCCCCT
CCGTTTATAGAAGGAAATCACTCCTCTCGGTGGTTGTACGAAGCGATGGCAAAAGCCTGGGAGCCGTG
GCTCCCTGCAGAAGCATTGCGGACATTGAGAATTGGCGGGTTTTACGCCCTGTCCCCTTATCCAGGCT
TGCGGCTCATATCTTTGAATATGAACTTCTGCTCTCGGGAGAATTTCTGGCTTCTGATCAATTCTACC
GACCCTGCAGGACAACTTCAATGGCTTGTAGGCGAACTGCAAGCGGCCGAAGACCGCGGTGACAAGGT
GCATATAATCGGCCACATTCCGCCTGGGCACTGCCTTAAAAGTTGGAGTTGGAACTACTACCGGATCG
TTGCACGGTATGAAAACACTCTTGCAGCGCAGTTCTTCGGGCATACGCATGTTGACGAGTTCGAAGTA
TTTTACGACGAGGAAACTTTGAGTAGACCACTCGCCGTTGCATTCTTGGCGCCGTCAGCTACAACTTA
CATAGGTCTGAACCCAGGGTACAGAGTATATCAAATAGACGGGAATTACAGCGGCAGTAGCCATGTAG
TCCTGGACCACGAAACATATATACTCAACCTTACCCAGGCAAACATTCCGGGCGCGATTCCTCACTGG
CAACTGCTGTACCGCGCACGGGAAACTTATGGTCTCCCCAACACACTTCCGACAGCCTGGCATAACCT
CGTGTACCGCATGAGAGGGGACATGCAGCTTTTCCAGACATTTTGGTTTCTGTACCATAAGGGGCACC
CCCCTTCTGAGCCTTGCGGTACACCCTGCCGCTTGGCCACCCTTTGTGCTCAACTCTCCGCACGGGCG
GATAGCCCTGCATTGTGTAGGCATTTGATGCCAGATGGGAGCTTGCCTGAAGCCCAAAGTCTGTGGCC
ACGGCCCCTGTTCTGTGATTACAAGGATGATGACGATAAGTA
The HEXB protein sequence is:
(SEQ ID NO: 16)
MELCGLGLPRPPMLLALLLATLLAAMLALLTQVA
LVVQVAEAARAPSVSAKPGPALWPLPLSVKMTPN
LLHLAPENFYISHSPNSTAGPSCTLLEEAFRRYH
GYIFGFYKWHHEPAEFQAKTQVQQLLVSITLOSE
CDAFPNISSDESYTLLVKEPVAVLKANRVWGALR
GLETFSQLVYQDSYGTFTINESTIIDSPRFSHRG
ILIDTSRHYLPVKIILKTLDAMAFNKFNVLHWHI
VDDQSFPYQSITFPELSNKGSYSLSHVYTPNDVR
MVIEYARLRGIRVLPEFDTPGHTLSWGKGQKDLL
TPCYSRQNKLDSFGPINPTLNTTYSFLTTFFKEI
SEVFPDQFIHLGGDEVEFKCWESNPKIQDFMRQK
GFGTDFKKLESFYIQKVLDIIATINKGSIVWQEV
FDDKAKLAPGTIVEVWKDSAYPEELSRVTASGFP
VILSAPWYLDLISYGQDWRKYYKVEPLDFGGTQK
QKQLFIGGEACLWGEYVDATNLTPRLWPRASAVG
ERLWSSKDVRDMDDAYDRLTRHRCRMVERGIAAQ
PLYAGYCNHENMDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HEXB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
HEXB DNA (SEQ ID NO: 17)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGGAATGAAGTCCTCAAGAACCTGCCTGTCC
AAGGATTCCTAAGGAAGCTGTTTATCCCGCTGTTTATCCCCAGAGGGTAAACTGTGTGGCTGGTTGCA
GTATCTGTTCCAGACACATAACAGCCAGTCCCAAAAGCGCAGCTGAAACTCTGTTTCCTTTAACCATT
CAGACATTTTTAAATGCATATTCTAAGAATTATTAATAAATGCAAATGAATGATTTGCCACAGATTCA
TGGGCTAAAATACTAACCTGCACCTCCCCAACCAGATGTGAGCCCCACTATAAGACTGCACAGAAAAC
CACAAAGGCAGGGGCATGACACATATACCTCATACCATTAGGTGATGCAACTAGTTTTCTTTCCTTTT
TGGAATATAATTTTTTATGATGAGTAAACATGGCTGAGTGGAAGAAAGGAAGCAACAAAGTCCTAGAG
CTCCAGTGTTAGGAAGACTTTACAAAGCACCCAGTAATTTCCACAGTGACTTGAGATATAAAAAATGG
TGAGGAGCCAGCTTCACTCCCACCTCAAGCTAAGCATCTACTGTCTACTCCATTCTAACCAATGCCCA
GTGTTTTGGAGAATGACCATATGAACCTATGGGAATGCATCAGGTTTCCAAAGGGTTAAAACATTCAT
TAGCATTCTCAATGCTCCACCACTGTAGTTGCTATTTTAATTAGTACATTCAATCTGGAGTATCTGGA
GGAAGACTTTAAACCTAAACCTCAATAGACTGTCTACTTACTCTTGTGAATCTGCCGCCTCTCTCAGA
GCAAATGCTGCCCTGAGTGAAGGAAGAATGAGGCTCCCTGAAACTAGGTGCACAGGCACCAAAATGCT
TACACATTGAGCTGGAATCATGCTAGGCCCAGAACACATTTCCTTGAACATTAAATTCAGGATGGTGC
AAAACAACATTCACAACCAGACTTACACCTAAGAAAACAATTTGCTTAGAAGACCTTAGGATATAGGA
TCTACATCTCTCCGCATCCTGTGTTTATGCTCCTGTATGTTCCAGGTTGGCCCAACAAGCCAGAAGGA
AGAGCCTAGCCTGTCATCTTGGATACCACCCAGATGGAAAAGCACGTCACAGTCAAAATCACAATCAA
CATTCTTGCAACAATGTTTGATTAAAATAAAAAGTAAACTTGGAAACCCAAGAGGAAATACTTGCTTT
CTGGTTTAAAACTGTGCAAACCTCAAAATATCAGCAGAAACCATGTATACAAGTCACTGAACACACCT
TCAACATAAAATGAATCATCTTTCGAGCATTTTTAAGCCCCCAGAGAAATCACATTTGCATACCAAGT
AAGTGGCCAAGAAAATGCACACATGTACTTAACCTACGTCTGCAAAGAAGACAGAGAAAGGGCTGCTA
TTACTGTGAACATCAAAAGGGCTTCAGTTACAGTAACTTCAGTTCACTTCATGCTCCTAACTCAGGCT
CTCTGCCTCCAATGCTTAGCGTCCCGCACCCTTCTCCAGGTTTTGAACCTGATCTCAATCCAATCAAA
AGAGAAACTAAGCAGATTTTTTTCTGGGCATTTACATTACCGGTAACAATAGAACATTATAAAGATCT
TGTTAACAAAAGTAGCTTCTTGCCAGAGTCTTTTTATTAACACTTGCAACGCTATTTAACAAGCTGGC
CATGCCTGTGTGACACCAAACCGCATGTGGATAAATTCAGTGTTTCATCTCCAGGCCCACCAATTCCT
ATCCTTTGTAACTAATAATGTTAACACGACAGATCAAGAAACTAGTTTTTCAGAAAGCAGTTTTCATT
CATTCTCTATAGACATTTCCGCCGCAGTGAACATGCCCGCACTCAGGGTGTCTGTGCATGGCCCCAAC
TTTCCTCCAAGCCGGGGAGGATGCAACGTGGGCCAACCATCCCGCGCGCTCGGCCCTGGAGGCTGCGG
GGAGCGACGCAGCGCGACATTCACCCCCAGGAAAGCGCTGCTTTCCGCAGAGGAGAGAGGCTGAC
ATGGAGCTCTGCGGACTGGGTCTGCCTCGCCCGCCTATG
CTTCTCGCGCTTCTGTTGGCCACTCTTCTCGCTGCGATGTTGGCTTTGTTGACACAGGTTGCTCTCGT
AGTCCAAGTGGCAGAGGCCGCCAGGGCACCGTCCGTGAGCGCTAAACCCGGGCCCGCTTTGTGGCCGC
TGCCTTTGTCTGTTAAAATGACTCCAAATTTGCTCCACCTTGCCCCGGAGAACTTTTACATAAGCCAT
TCTCCCAACAGTACCGCAGGGCCGTCATGCACTCTTTTGGAGGAAGCATTCCGCAGATACCATGGATA
TATCTTTGGTTTTTACAAGTGGCACCACGAGCCGGCCGAGTTCCAAGCTAAAACCCAAGTGCAGCAAC
TGCTCGTATCTATTACACTCCAAAGTGAGTGTGACGCCTTCCCCAATATTAGTAGTGACGAGTCATAT
ACCCTCCTCGTTAAGGAGCCCGTTGCTGTTCTGAAAGCTAATCGGGTCTGGGGTGCTCTGCGAGGCTT
GGAGACTTTCAGCCAACTGGTGTATCAGGACTCATATGGCACCTTTACGATTAATGAGTCTACGATCA
TTGATAGTCCCCGGTTCTCCCACCGCGGTATATTGATTGATACATCCCGGCATTACTTGCCAGTCAAA
ATCATTCTGAAAACGCTGGACGCTATGGCGTTTAACAAATTCAACGTTCTTCATTGGCATATAGTAGA
CGATCAATCATTCCCTTATCAGAGCATTACCTTTCCAGAACTGTCTAACAAGGGATCTTACTCACTCT
CACATGTGTACACGCCTAATGACGTTAGAATGGTGATTGAATACGCGCGATTGAGGGGTATTAGAGTT
CTCCCGGAGTTCGACACACCTGGCCATACTCTCAGCTGGGGCAAGGGTCAAAAGGACTTGCTTACACC
TTGTTATTCCAGACAGAATAAACTTGATTCATTCGGTCCCATTAACCCTACGCTGAATACTACATATA
GTTTCCTTACTACGTTCTTTAAGGAGATAAGTGAGGTTTTTCCCGACCAATTCATTCATTTGGGAGGT
GACGAGGTGGAATTTAAGTGCTGGGAAAGCAATCCAAAGATTCAAGACTTTATGCGGCAGAAGGGTTT
TGGCACCGACTTTAAGAAACTTGAATCCTTTTACATTCAGAAAGTTCTGGACATAATCGCCACAATTA
ACAAGGGTAGTATCGTGTGGCAGGAGGTATTCGATGACAAAGCTAAACTGGCCCCGGGAACTATCGTA
GAAGTCTGGAAGGATTCCGCTTACCCGGAGGAACTGAGCCGCGTCACAGCGAGTGGCTTTCCTGTGAT
ATTGTCAGCACCTTGGTATCTGGACCTTATCTCCTATGGGCAAGACTGGCGCAAATATTATAAGGTTG
AACCTCTGGATTTTGGCGGGACTCAAAAACAAAAACAACTCTTCATCGGTGGCGAAGCCTGTCTGTGG
GGTGAATACGTAGACGCTACGAATCTCACTCCCAGACTCTGGCCACGAGCCTCTGCTGTCGGGGAACG
ACTGTGGTCTTCAAAAGATGTAAGGGATATGGACGACGCCTATGACCGGCTGACTAGACACAGATGTA
GAATGGTAGAGAGGGGAATTGCTGCACAGCCGCTTTACGCCGGGTATTGCAATCATGAGAACATGGAT
TACAAAGACGATGACGACAAATA
The SGSH protein sequence is:
(SEQ ID NO: 18)
MSCPVPACCALLLVLGLCRARPRNALLLLADDGG
FESGAYNNSAIATPHLDALARRSLLFRNAFTSVS
SCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFD
KVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDF
AYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRP
FFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGM
GRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAA
QYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTS
DNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWG
QVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKT
IHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSY
PMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTF
QDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRS
RDPHETQNLATDPRFAQLLEMLRDQLAKWQWETH
DPWVCAPDGVLEEKLSPQCOPLHNELDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SGSH and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
SGSH-DNA (SEQ ID NO: 19)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGCACAGTCTCGGCTCACTGCAAGCTCCGCCT
CCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCAGGTAGCTGGGACTACAGGCACCCGCCACCACA
CCTGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCCTGTTAGCCAGGATGGTCTCCATCT
CCTGACCTTGCGATCCGCCTGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCTTGAGCCACCGCACC
CAGCCTAATTTTTGTATTTTTAGTGGAGACGGGGTTTCACCATTTTGGTCGGGCTGGTCTTGAACTCC
TGAGGCCTCCATGAGTCATCTCGCTGGCCCCTCCATAACCAGCTCAGTGTCTGTGTGTGCCAAACAGG
CATAGGAGCCTGGGTCGGCCCAGAGACAATCTGCGTCACACACTGTAAACCAAAGGTTCCTTGGGGCC
CAGGGGCTGGAAACCTGGAATCGCTGATGGTGTCTGGGATTGATACTGTGTATTCTGCACTGTTTCTG
AGATATGGCTGGCAGCAGGGTCAGACGCCTCACCTGGGGCGGGAGTCCAGCCACTTCAGCATAGGCCA
GCGCCTGGGGAATGGCAGTGAGGCCAACTGAGAGGCCGGCGACGAAATCCATCTTCAGCCACTGCAGG
GAGTAGCTGGGCAGCCACGCCAGGATGGGCAGCCTCCTCTGCAGGGCCGCAGGGGAGCAGCAGCAGGC
GCTCGGGGCCATCCCGGGGCCAGAGGACCTGGCCTGACCCAGCGCCGTCACCGAAGAAGGCATCTCTA
CGGTGGGGCTGGGGGGTGCAGGTGACACAGACCAGCAGTCAGAGCGTGGCCTTTGAAGAACCCGGCAA
CACTGGTCAGGGTCGGCGGGTGTCAGGAGAGGTCACTATGGGTCTCCCCTCCCCAGGGGGGCGAACGG
CTCTAAGAGGAAGCCAACAATGTGTGCAAGATGGGGACTGGGCCAAGACTGGAAGGCCCACCCCGTCC
CTCATCACCCTCTCTCCCTGAATCCCCCCCGTGCAAATCCTGGGTGCCTTCTGTCCCTCCATCCTCAA
CTCTCCCAGATAAGAAACTGATAAGCGATTCCTCATTGAGAAGTCTGAAGACTAATTAGGCTCAACAC
TTCTGGCCCCTGGAGAACCGACTTCCTTTGCCTTTTTTTCCGTCTCCCCAGGGAATTTAACGGGGAGC
AGCGCAGAGAGAAGCTGGGCCCGCGGGCGCACCGTAGGCTGGCGGGGGGTGCGGGTGGCAGCCAGGAG
ATCCAGCGGGGCTCCGAGGTTTTCCAACTGCGCACCAAGGCGGGCTCCACCCGCTACGGTGGACTGCG
GCGCTCGAGGGAGAGTGGGGGGGTCCTCCGCTCCTGAGGCCACGCCTCGCTCAGCCCCCACCTGTGGC
TTTCACAGCCCTGGAGTTCTAGTTGCTTCTGGGAGGACATCAGAGGCGCCCGGTTAATTCAGGTGCGC
AGCATCTTCCAGGGCCCCGGCGCCCGCGCGCAGAGCCGCCACCCTCACCCCCAGCCCCCCACGCCCCC
GGCCGCTCCGCTCCGGGCAAAATCCACTCCCCGGCCCCCGGCCCCGCCCACAAGGCCGCTGGCTCCGG
ATCCTGGGGTCTCCGGAGGAGACCCTGCGCCACCTGACCGTCCGCGGTCCCTTGGCCCCGAGCAAGGC
CGAGGGCCGCGGGGACCCGGGTAGGGACGCGGCGGGGGAGTGGTCCCCACGGGAGGCCCCCGCACTTC
AGGACTCCGCGCTGGCCCCCGCGTCGGCTGCCCCCGGCGACCCCGGCCACTGTCCGCTCCCCCTGCCC
CTGGTCCCCGCTCGCCGCCCTCGCGGGCCACGGACTCACCCACTCGGCGATGCAGCTTGGGGTCTCCT
GGCGTCGCCGCAGCTGGGTCCGCAGGAATCGCCGGGGACAGGCCGGGGCGGGGTCTGGCGCGCACGTG
ACCGGGGTCGGGGCAGGGGGCGGGGCCGAGCGGGAGACCAGAGAGCCGGAGCCGGATCCCGATCC
ATGTCTTGCCCGGTACCGGCCTGCTGTGCTCTCCTTCTG
GTCCTCGGTCTGTGTCGCGCTCGCCCCCGAAATGCGTTGCTCTTGCTGGCCGACGACGGGGGCTTTGA
AAGCGGTGCGTATAACAATAGTGCTATCGCAACCCCTCACCTTGATGCACTCGCACGCCGGTCTCTCC
TGTTCAGGAACGCCTTTACATCCGTCAGTTCTTGTTCACCTAGTAGGGCTAGTCTCTTGACAGGCCTC
CCCCAGCACCAAAACGGGATGTACGGACTGCATCAAGACGTGCATCATTTCAACAGTTTCGACAAAGT
TAGATCCTTGCCCCTCTTGCTTAGCCAGGCGGGTGTGAGGACCGGCATAATTGGAAAAAAACATGTGG
GGCCTGAGACTGTCTACCCTTTCGACTTCGCTTACACGGAGGAAAATGGTTCAGTCCTGCAAGTAGGG
AGAAACATTACCAGAATTAAATTGCTTGTGAGAAAATTCCTGCAAACCCAAGATGATCGCCCATTTTT
TCTGTATGTCGCCTTTCATGACCCTCACCGCTGTGGTCACAGTCAGCCTCAATACGGTACATTCTGTG
AAAAGTTTGGCAACGGGGAAAGTGGCATGGGCCGGATTCCTGATTGGACACCACAAGCGTATGATCCA
CTGGACGTCCTTGTCCCGTATTTTGTTCCAAACACCCCGGCTGCTCGGGCAGATTTGGCAGCACAATA
TACTACTGTCGGGCGAATGGATCAGGGAGTTGGTCTCGTTCTGCAAGAGCTGCGGGACGCAGGTGTCC
TGAACGATACGCTGGTAATCTTTACCTCAGACAATGGTATCCCGTTCCCATCAGGGAGGACGAACCTT
TACTGGCCTGGTACTGCAGAGCCTCTGTTGGTGTCCTCCCCAGAACATCCCAAGAGGTGGGGCCAGGT
GTCCGAAGCTTATGTTTCTCTTCTTGACCTTACCCCGACCATACTTGATTGGTTTTCCATCCCCTATC
CGTCTTATGCAATATTTGGTTCTAAAACGATACATCTTACCGGCCGATCTCTTCTGCCGGCGTTGGAG
GCGGAACCCCTGTGGGCCACTGTATTTGGTTCACAAAGTCACCATGAAGTCACGATGAGTTACCCGAT
GCGAAGTGTCCAGCACAGGCACTTCCGACTCGTGCATAATTTGAATTTCAAGATGCCGTTTCCAATCG
ACCAGGATTTTTACGTAAGCCCGACTTTCCAAGACCTGCTGAACCGCACAACAGCGGGTCAACCAACG
GGGTGGTACAAAGATTTGCGCCACTACTATTATCGAGCTCGATGGGAGCTGTACGATCGGAGTCGAGA
TCCTCATGAAACTCAAAATCTGGCGACAGATCCTAGATTTGCGCAGCTCCTGGAGATGCTTCGGGATC
AGCTTGCGAAATGGCAATGGGAAACCCATGATCCTTGGGTGTGTGCGCCAGATGGTGTACTCGAGGAG
AAACTGTCCCCGCAATGTCAGCCCCTGCACAATGAGCTTGATTACAAGGACGACGACGACAAGTA
The HEXA protein sequence is:
(SEQ ID NO: 20)
MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSD
QRYVLYPNNFQFQYDVSSAAQPGCSVLDEAFQRY
RDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTP
GCNQLPTLESVENYTLTINDDQCLLLSETVWGAL
RGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHR
GLLLDTSRHYLPLSSILDTLDVMAYNKLNVFHWH
LVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQD
VKEVIEYARLRGIRVLAEFDTPGHTLSWGPGIPG
LLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL
EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMR
KKGFGEDFKQLESFYIQTLLDIVSSYGKGYVVWQ
EVFDNKVKIQPDTIIQVWREDIPVNYMKELELVT
KAGFRALLSAPWYLNRISYGPDWKDFYIVEPLAF
EGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPR
AGAVAERLWSNKLTSDLTFAYERLSHFRCELLRR
GVQAQPLNVGFCEQEFEQTDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HEXA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
HEXA-DNA (SEQ ID NO: 21)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGCCATCTCAAAAAAGAAAAAAATAAAGAGAG
ATGGGATTTCCTCGTATTACCCATGCTGATCTTGAACTCCTGGGCTCAAGTGATCCTCCCATCTTGGC
CTTCCACAGTGCTGGAATTGCAGGTGTGAGCCACCATCCCCAGCCTGTGATCCATTTTTAATTAAGTT
TGTGTATGCTGTGAGGTAGGGGATCATAGTTCATTTTTCCCACATAGGGATATCTATTTTCTTCATCA
CCTTTTATTGAAAATAACTTGCCTTCCCCACTAAATTAAATTGGTGTCTTCATTGAAATGGAGTAATA
ATCAAATGGCTCTTTTCCTGGACCCTCTATTCCGTTCCATCTATTTGTCTGCCATTATGCCAAAACCC
CACTCTAGTGTATAGTAAGGGGGGATATTTTGGAAGATCAACAAATTTATCTTGTGTAACTTACTTTT
ATGTATGCATAAGAATATTTGGTTTAAAAATCTGGTTAAGTCTAAAAGAGCTCTTTCAGTAATAATTA
AATAACTGAATCCCTGTAATCCACCATGCTCAGCCCCATTAGTAATTTTTATAGCGTCTTTATTTGGA
TCTAGCTCTTTCATCTTGTGTAACTCTTTTAAGTAAATGACTCCTCCCTTCTGGTACAGGTTGAATAT
CCATAAAAGGGTGCCTTGGCATGTGCTCAGTCCTGAAATTCTACTTTGATCTACTGCTCTCATCTTTG
AAACTGCTCTAAACACTCCCCCAAATTATTGATCCTGTGGGCCTGATTATGAACTTGGCTCTTCTGAC
AATACTTCTCAAATCCTGTACCTTTGGTAACATCTCTCCTGACTGGCAGAGTACCCAGACACTTAATT
AATGCTGATGAAAATTAAGATTTAAGCAAAGAAGAAATTGGTGTAAGAATGCAAGCCTTAGGATCTGA
AACTTGATGACTGTGGGATCTAATTTCTGCTTCTTTTGCTACAAGCTCTGTTTTTGAATAATCAACTT
TCAAAGACAAATTGCTTGATGAATCTCTGTATTGTCAGAATGTTTCTTTGATTTCCCATCAAAGCCAT
GTATGTGTAACTAGTAATTAGGTACCTACGACCTGAATATAAATTATCATTATTTCAGTAGCCCTTTA
TTTGTTTTTGAGAAAGGGTTTCACTATACTGCCCAGGCTAAACTTGAACTCCTTGGTTCAAGTGATCC
TGCCGCCTCAGCCTCCTGAATAGCTGGGAGTAGCTGGGACTACAGGGATGTGTTATCATGCCCAGTGA
AAGCCCTTTATTTTTAAAAGTTCATTTTCCTGATCTTTACATGTATTTTAATACTAAAATTAAATTTA
AAAATTTTAAAAAGTACCTACTAACCAAATAATGCCACCCAATAACAATAGCATTATTTGTATTATGT
TCTGGTAATATAGTGGTGAACAAGGAAGACAGGGTCTCTGATAACTGTGGAATTCTCCTTGATCACTT
CTCAAGCCTCTCTTCCGGATACTATTTCTTGGATCTACAGCTGTCTTCCTTCCCCACTTCTGTAGTTC
AGTCTCTCATTATTCTCTACCTCCAATAAAAAGGGGCCTCCTAACTGGTTTCTTATGCAACTACTCAA
CATGGTATTTCTAAAATGCAGATCTTTCGGGATGATTTTCAATTGCTCAGAGAATAAATTCCTTGACT
TTCTACGTAAGGCCCTGCAGGACCAGGCCCCTGTCATTATCTCTGAGCACTCTCCATCTTGCACCCAA
AGCCCCAGCAATATCTTACTGCTTTCAGTAAATACACACCGGGCTATGTGGGGTTTTGTCTGGGGAAA
GGGGATGTGAGTTGTAACTAAGAGATTTATAGTCAATCTTGAAGGGAAGAGCTCATATTGGAGGCAAT
GGAATGCCTCAAGCTGGCTCTGAAAGTACACATTTTTTCCAGTCATAAGTAGATCACATTTGTGTGAT
CTTGTGATCCTCTCTCTAGCAGAGCCGTGCAGACTACCTACTTCCGGCCCTTTCTTGCCCCACGAAAT
TTCACATCACAACGACTTGTGGTTTTAATCCTCCGTTTTTCTGCTTCTGAAGTTACTTCAGCCTGGCA
AGTCCTTTACCTCCCCGTAGGCCTGGCGAGCTGCATCACAACATTCAAGATTCACCCTAGAGCCATCT
GGGAAACTTTCTTCTCCAGGTCGCCCTGCGTCCTCGCCTCCCCACCCCGTTCTTCTCGAGTCGGGTGA
GCTGTCTAGTTCCATCACGGCCGGCACGGCCGCAGGGGTGGCCGGTTATTTACTGCTCTACTGGGCCC
GTGAACAGTCTGGCGAGCCGAGCAGTTGCCGACGCCCGGCACAATCCGCTGCACGTAGCAGGAGCCTC
AGGTCCAGGCCGGAAGTGAAAGGGCAGGGTGTGGGTCCTCCTGGGGTCGCAGGCGCAGAGCCGCCTCT
GGTCACGTGATTCGCCGATAAGTCACGGGGGCGCCGCTCACCTGACCAGGG
ATGACGTCTAGCAGATTGTGGTTCAGTCTGTTGCTCGCCGCGGCGTTTGCCGG
CCGAGCCACCGCATTGTGGCCCTGGCCCCAGAATTTTCAAACTTCCGATCAAAGATACGTCCTCTATC
CTAACAATTTCCAATTTCAATATGATGTGAGTTCAGCTGCACAGCCGGGATGTAGCGTCTTGGACGAG
GCGTTCCAAAGATACAGAGATCTCTTGTTTGGCTCAGGCTCATGGCCACGGCCGTACCTTACTGGCAA
GCGGCATACACTTGAAAAGAACGTGCTCGTCGTAAGTGTAGTAACTCCGGGTTGTAATCAGTTGCCCA
CGCTCGAGAGCGTCGAAAACTACACACTCACGATTAACGACGATCAGTGTCTGCTCCTTTCAGAGACC
GTATGGGGGGCGCTGAGGGGCCTTGAAACATTCTCACAGCTTGTTTGGAAATCAGCGGAGGGAACGTT
TTTTATCAACAAAACGGAAATAGAAGATTTCCCCAGATTTCCACATAGGGGCCTGTTGCTGGACACCA
GTCGCCACTACCTTCCACTCTCATCCATACTTGATACCTTGGACGTAATGGCCTATAACAAACTGAAT
GTTTTTCACTGGCACCTTGTAGATGATCCATCCTTCCCTTACGAAAGTTTCACTTTTCCCGAGCTCAT
GCGGAAGGGCTCCTATAACCCTGTTACACATATATATACAGCTCAAGATGTAAAAGAGGTGATCGAAT
ACGCACGCTTGAGGGGGATACGAGTGCTCGCTGAGTTTGACACACCAGGTCACACACTTAGTTGGGGG
CCTGGCATTCCTGGGCTTTTGACACCCTGCTATAGCGGATCAGAGCCCTCAGGGACTTTTGGACCTGT
GAATCCATCTCTGAATAATACGTACGAATTTATGAGCACATTTTTCCTGGAGGTCAGCTCCGTGTTTC
CCGATTTCTATCTGCATCTGGGAGGCGACGAGGTGGATTTTACCTGTTGGAAATCCAACCCCGAAATC
CAGGATTTCATGCGGAAGAAGGGCTTCGGTGAAGATTTTAAGCAACTCGAGAGTTTCTACATACAGAC
CCTTCTTGATATCGTCTCTAGCTACGGTAAGGGGTATGTTGTATGGCAAGAAGTATTTGACAACAAGG
TAAAAATACAGCCCGACACCATAATCCAGGTCTGGAGGGAAGATATCCCGGTTAATTATATGAAGGAG
CTCGAGTTGGTTACAAAAGCAGGTTTCCGAGCGCTTCTCTCTGCTCCTTGGTATCTGAACAGGATCAG
TTATGGTCCGGATTGGAAGGACTTTTATATAGTTGAGCCATTGGCATTTGAGGGGACACCTGAACAAA
AAGCTCTTGTCATCGGAGGGGAAGCCTGTATGTGGGGCGAATACGTAGATAATACGAACCTCGTGCCG
CGATTGTGGCCCAGGGCCGGGGCGGTAGCGGAAAGGTTGTGGTCAAACAAACTTACGTCAGATCTCAC
CTTTGCCTACGAGCGATTGTCCCATTTCCGCTGCGAATTGCTCAGGCGGGGAGTCCAAGCCCAACCCC
TCAATGTAGGTTTCTGCGAGCAGGAGTTCGAACAAACCGATTATAAAGATGACGATGACAAATA
The IDS protein sequence is:
(SEQ ID NO: 22)
MPPPRTGRGLLWLGLVLSSVCVALGSETQANSTT
DALNVLLIIVDDLRPSLGCYGDKLVRSPNIDQLA
SHSLLFQNAFAQQAVCAPSRVSFLTGRRPDTTRL
YDFNSYWRVHAGNFSTIPQYFKENGYVTMSVGKV
FHPGISSNHTDDSPYSWSFPPYHPSSEKYENTKT
CRGPDGELHANLLCPVDVLDVPEGTLPDKQSTEQ
AIQLLEKMKTSASPFFLAVGYHKPHIPFRYPKEF
QKLYPLENITLAPDPEVPDGLPPVAYNPWMDIRQ
REDVQALNISVPYGPIPVDFQRKIRQSYFASVSY
LDTQVGRLLSALDDLQLANSTIIAFTSDHGWALG
EHGEWAKYSNFDVATHVPLIFYVPGRTASLPEAG
EKLFPYLDPFDSASQLMEPGROSMDLVELVSLFP
TLAGLAGLQVPPRCPVPSFHVELCREGKNLLKHF
RFRDLEEDPYLPGNPRELIAYSQYPRPSDIPQWN
SDKPSLKDIKIMGYSIRTIDYRYTVWVGFNPDEF
LANFSDIHAGELYFVDSDPLQDHNMYNDSQGGDL
FQLLMPDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for IDS and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
IDS-DNA (SEQ ID NO: 23)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGAAATAAGATCACATTCTGAGGTACTGGGTG
TTAGGACTCCAACATACAATTTTTGGGGGGAGGACACTAACACCTAAGTCAAAAAGGACCAAAAGACA
TACCATACAAAGCAAAGGCCCTCTGCCCTGCACCTTCCCTCTTCTGTTCTCATTTTAAATGTTTCTAC
TTTCATTTCTTCTAGTAGATTGTCCCTGTCTTTCTAAATACTATGCTATTTCTATATCAACTTTCTAA
TGTTTTCAACTTTAGACATTGCTGACTTCTTCCTATGATAGATGAGATCACTTATCCATTCCTCTTTT
TATGTACATATTTTTAACCTTGGATTTTGGAAATTGATCAAACCTATACAAGATTACAGAAAATAGTA
TAATAAACCCCAGGTGTTCATCAATGAACTTCATTGGTTATCAACTCATGACAAATTTTGTTTCATCT
CTCCCTGCCATTTTCCCTTCTCCTTTTACTATATAGATTTATTGCCATTTTTAAGTTTTCTATTGTTT
ACTTTTGTATCTTTAAGTAATATCCCTAAATCTGTATTTCTCTTTCTATGAACTGGGGACAGCGACTA
TTGATTTATTATTATTATTATTATTATTTTTTTGCGATAGGCTGGGGCAAAGGAGACAATCCTAAATT
GCTAACCCTAAATTAATGTGCCTACATTTCCTGCCATCTCCCTTCCTCCTCCCAGCTTTTTGTCAACT
GTTGCTGCAGGCCAGGTTCCCAAGGAAGCTGACTAAGATGTAGAGTAATGTGCAGGAAGTTTCTTAGG
GAGTACTCTTAGGATCAACACCTGTAGAAGGGGAGGGGAGGGAAGAAATCAAAATTCAACAGACAGAG
AAAGTGGGCAGTCTCAAAAAAGGCTTCAGTTAACCCCACAGGGAGCTCTGAAGCTGAAATGGCCTTTC
AGAGATGTCCCAAGTTGGGGTAAGGGGCTGCACCTTTGTACCTTCAAGTTGAATCACTGATGTGGGCT
TCCTGAGAACAGGGGTGACCTTGGCTGAGGTACCTATCTTTTTCTAAGACAATTTCTGATGAGGGCTA
ACGACAGCTAACAGCTCTCAAGCCAGCTAGGGAAATAAAATTTTTGGTGTTGAAGGGAGATCTGAGCA
GTGCACCACAGCACCATCACAGCTGTATTTGTACCTTCCCATTGTCCATTGTTGTTTAGTCATAATTA
AGTCATCTGGGCTTTGTTATAGATTGATTCTCAAAGTTGAAAATCAAACTGTGTTTGCAGTATTAGGA
CGGTATAATAGTATTCAGTACAGTACAGTGTAGGGCTAGGATTCCATCTCCCCACAATTGCTGCTCTC
TCTGTTTGGCGCACCCTTCTTGCAGACCTCAATGCGGCTTGCTCCCTCACTTGCTTCAAAATTTTGTT
CAAATGCCACTTCACTAGTGAGGCCCTGCCTGGCCACCCCATAGAAAATAACAAGCATGCCCCGCACC
CACGCTTTATTTTTCTCCAGACCGGGTATGCCCACCGACACTCTCTATATTTTTTTATTGTTTTAAGC
TCCACCAAAGCAGGGACATAGAGCCCCAGTGCCACCAACAGCGCCTGGTATACATATTTGCGATACTT
AATAAGAATTAGTTGAAGAAATGAATAGGAAAGGGAGTCCCTTTAGATGGAGGAAGGGACTTTCTCAA
AAGGCCTCATGGAAGGAGAATGGCATTGAGGCTGGCTTACAAGAAGTGTGTCTTTTATAAAAAGAAGG
AAGGGCAGGGCTTCCAGGTGAAAGGCATAGCACAAGCAAAGGCAAAAAGACGGGTAACTGCTAGTTGT
TAAGGGCAGTGGCTGAATCGCTATACCCCTAGCAGTTCTACACCTAGGGGCCTGCGGGCCGCTGGGTC
TGCGAAGCTTGCAAGGCAACTGGCCCGCCCCCGCTCTGCGCCTGTCTCTCGGCCACGCCTATTGCTGC
AGGATGACGCGCACCTCTAGAACCCGCCCCGGAGGGGAGGGACGCAGGGAAGAGTCGCACGGACG
ATGCCGCCTCCTCGGACGGGGCGCGGGCTTCTGTGGCTC
GGTTTGGTATTGTCTTCAGTGTGCGTGGCCCTGGGATCAGAAACTCAGGCGAACTCCACGACTGATGC
ATTGAACGTATTGTTGATAATAGTTGATGACCTGAGACCCAGTCTCGGCTGCTACGGTGATAAACTCG
TACGAAGCCCCAACATTGATCAATTGGCAAGTCATTCCCTCTTGTTTCAGAACGCTTTTGCCCAACAG
GCGGTTTGCGCACCGAGCAGGGTTTCCTTCCTCACAGGCCGCCGCCCTGACACTACCCGCTTGTACGA
CTTTAATTCATACTGGCGCGTCCATGCCGGTAACTTCTCTACGATACCGCAATACTTTAAGGAAAACG
GTTATGTCACTATGAGCGTAGGTAAGGTATTTCACCCGGGGATCAGTTCCAACCACACCGACGATTCT
CCTTACTCTTGGAGTTTTCCTCCATATCACCCAAGCAGCGAAAAGTATGAGAATACAAAAACTTGTAG
AGGCCCCGATGGTGAGCTTCACGCAAATCTGCTTTGCCCAGTCGATGTGCTCGATGTCCCAGAGGGCA
CTCTGCCGGATAAGCAATCCACGGAGCAGGCTATACAGCTGCTCGAAAAGATGAAAACTTCAGCGAGC
CCGTTTTTCCTCGCGGTGGGTTACCACAAGCCGCATATCCCGTTCCGGTACCCTAAGGAGTTTCAAAA
ACTTTATCCGTTGGAGAATATCACACTCGCGCCCGACCCCGAAGTCCCAGATGGACTTCCTCCGGTCG
CTTATAATCCCTGGATGGACATTCGCCAGAGGGAAGATGTACAAGCTCTCAATATCTCTGTTCCATAC
GGGCCCATTCCGGTTGACTTTCAGAGGAAGATTAGACAATCATACTTCGCCAGCGTATCCTATCTTGA
CACCCAAGTTGGACGCCTGCTCTCCGCGCTTGATGACCTGCAACTGGCAAACAGTACCATAATAGCCT
TTACCAGTGACCACGGTTGGGCACTCGGAGAACATGGAGAGTGGGCCAAGTATAGTAATTTTGACGTG
GCTACCCATGTACCATTGATTTTTTATGTTCCCGGCCGGACAGCTAGTCTCCCGGAGGCTGGAGAGAA
ACTGTTTCCATACCTTGACCCCTTTGATTCCGCGTCTCAGCTTATGGAACCGGGCCGCCAAAGCATGG
ACTTGGTTGAACTGGTTAGTCTCTTCCCGACGTTGGCTGGCCTTGCAGGGCTCCAAGTTCCACCGCGG
TGTCCCGTACCTAGTTTCCACGTTGAACTCTGTCGGGAGGGGAAGAACCTCCTTAAGCACTTCCGCTT
TCGGGATCTTGAGGAGGACCCCTACTTGCCAGGTAATCCTAGAGAGCTGATAGCGTACTCCCAGTACC
CACGACCGTCTGATATTCCACAGTGGAACTCCGACAAACCTAGTCTGAAAGACATTAAGATCATGGGC
TACAGTATTAGAACGATTGACTACAGGTATACCGTGTGGGTCGGCTTTAATCCAGACGAATTTCTCGC
GAACTTTAGCGATATCCATGCGGGTGAGCTTTATTTTGTTGATTCCGATCCGCTCCAGGATCATAATA
TGTATAATGATTCACAAGGAGGTGATTTGTTTCAACTTCTCATGCCGGACTACAAGGATGATGACGAC
AAGTA
The NEU1 protein sequence is:
(SEQ ID NO: 24)
MTGERPSTALPDRRWGPRILGFWGGCRVWVFAAIFLLLSLAASWSKAEND
FGLVQPLVTMEQLLWVSGRQIGSVDTFRIPLITATPRGTLLAFAEARKMS
SSDEGAKFIALRRSMDQGSTWSPTAFIVNDGDVPDGLNLGAVVSDVETGV
VFLFYSLCAHKAGCQVASTMLVWSKDDGVSWSTPRNLSLDIGTEVFAPGP
GSGIQKQREPRKGRLIVCGHGTLERDGVFCLLSDDHGASWRYGSGVSGIP
YGQPKQENDFNPDECQPYELPDGSVVINARNQNNYHCHCRIVLRSYDACD
TLRPRDVTFDPELVDPVVAAGAVVTSSGIVFFSNPAHPEFRVNLTLRWSF
SNGTSWRKETVQLWPGPSGYSSLATLEGSMDGEEQAPQLYVLYEKGRNHY
TESISVAKISVYGTLDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NEU1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
NEU1-DNA (SEQ ID NO: 25)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGATCATGGTGAGTGACTCCCCTCTCTGCTGC
TCCACCCCCAACTCCCCAGAGGAACCCAATAACCCCAACGGGTCATGTCTTCCAGACCTCCATCCTGG
GGGCCTATGTCATCGCCAGCGGCTTCTTCAGCGTTTTCGGCATGTGTGTGGACACGCTCTTCCTCTGC
TTCCGTGAGTGACACCCCCAGCCACCTGTCCCCAACCTTAAAGTACTGAGCCGTTCAAGCATTTTTTT
TTTTTTTTGGAGATTTGGTGCTTCTAGAAAGAATGCCTTTGTGAGCTAAACGAACCAGAGGGAGCTTC
TTGTGACATCCTGAGGCCAGGCGTTTAGGGAAGAAGGAAGAGAGTGAGCCCCCAGGCCGGTAGGCTCT
CCAAAGAAGGAGCATTCTGATGGAGAGGTCTCTGCTATCTTCCCTAAGAAATCTCGGGTAGAAGTTAG
CCATTAGAGGCCAGGCATGGTGGCTCACGCCTGTCATGCCAGCACTTTGGGGGACCGAGGTGGGCAGA
TCACCCTGAGGTCAGGAGTTCGAGACCAGCCTGGCCCACATGGTGAAACCCCTCTCTACTAAAAATAC
AAAAAATTAGCTGGGCGCGGTGGCGGGCGCCTGTAATCCCAGCCACTTGGGAGGCTGAAGCAGGAGAA
TCGCTTGAACTCAGGAGGCGGAGGTTGCAGCGAGCCGAGATTGCGCTACTGCACTTCAGCTTGGGCGA
CAGCAAGACTCCGTCTCAAAACAAAGAAAAAAGATTAAAAAAAAAAAAGAGCCATTAGAGAGACTTCC
CAGCAGGTGGCTGTAGCGGCAGGGGATTTTCTTACTCTACAGCATGCATCCATTCAGGGTTTGCCAGT
CTCCTCCTAAGCGACTGACATGCATTTTTTCCGCTAATTCTTATCATCGCTCTATGCAACATAATATT
CCCGACCCCACTTCACAGGAGGAAACTGAGATTACATAACCTGCCCGGGGGTAAGGGTGGTGGTGCAG
CTTGGATTCCAAATCCCGCAGGCAGCTTGCCTCCCAGTCCCCGATTTCCTGGCCCCAGGGTCCGCTCT
AACCGGTCTCTGTTGCGGCTCAGTGGAAGACCTGGAGCGGAACAACGGCTCCCTGGACCGGCCCTACT
ACATGTCCAAGAGCCTTCTAAAGATTCTGGGCAAGAAGAACGAGGCGCCCCCGGACAACAAGAAGAGG
AAGAAGTGACAGCTCCGGCCCTGATCCAGGACTGCACCCCACCCCCACCGTCCAGCCATCCAACCTCA
CTTCGCCTTACAGGTCTCCATTTTGTGGTAAAAAAAGGTTTTAGGCCAGGCGCCGTGGCTCACGCCTG
TAATCCAACACTTTGAGAGGCTGAGGCGGGCGGATCACCTGAGTCAGGAGTTCGAGACCAGCCTGGCC
AACATGGTGAAACCTCCGTCTCTATTAAAAATACAAAAATTAGCCGAGAGTGGTGGCATGCACCTGTC
ATCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCAGAGGTTGCAGTGAGC
CGAGATCGCGCCACTGCACTCCAACCTGGGTGACAGACTCTGTCTCCAAAACAAAACAAACAAACAAA
AAGATTTTATTAAAGATATTTTGTTAACTCAGTAAATCTGTGACTCATTCTCTCCACGACGACAGGCG
GCCTTTTTTTTTCCGCGCCCGGCTCTTTAAAATCGGCCCCGCCCCTGTGACGTGTCCTGGTGCCGCGG
CCAATCAAAAAGCCCAATAAGGATGGTGCCAGTCCCTTCTTCACCCCAGCCAGTCCGCTTCCCGTTCG
GGTCACGCGCTCCGGGCCTCCAAGAGGGCCTCCAAGAGGGCCAATCGGAAGGGCAAGCTTCGAGATGC
TGCGTGATCACGTGGGAGGAGATGAGCTACTTGAAGACCAATTAGAGTCCGGGAAGCGCGGCGGGGCC
TCCAGACCGGGGCGGGCTTAAGGGTGACATCTGCGCTTTAAAGGGTCCGGGTCAGCTGACTCCCG
ATGACAGGCGAACGCCCTAGCACTGCATTGCCTGACAGA
CGGTGGGGCCCTCGAATACTCGGGTTCTGGGGAGGGTGCAGAGTATGGGTTTTTGCGGCCATATTCCT
CCTGTTGAGCCTGGCTGCATCCTGGTCAAAAGCGGAGAACGACTTTGGGCTGGTGCAACCGTTGGTTA
CGATGGAGCAGCTCCTGTGGGTTAGCGGCAGACAGATCGGGTCAGTAGATACGTTCCGAATACCACTG
ATCACAGCCACTCCGCGAGGCACACTCCTTGCTTTTGCAGAAGCCAGGAAGATGAGCTCATCAGACGA
GGGCGCTAAATTCATCGCATTGCGGCGATCCATGGACCAGGGATCTACATGGAGCCCGACGGCATTTA
TAGTGAACGATGGGGACGTGCCGGATGGACTTAACCTTGGAGCGGTTGTATCAGATGTGGAGACAGGC
GTTGTGTTTTTGTTCTACTCACTTTGCGCACACAAGGCGGGCTGCCAGGTTGCTAGCACTATGCTCGT
ATGGTCCAAGGATGACGGCGTGTCCTGGTCTACGCCACGAAATCTCTCACTCGACATTGGTACTGAAG
TATTTGCACCAGGGCCGGGTTCCGGTATCCAGAAGCAACGGGAACCTCGGAAAGGTAGACTTATAGTA
TGCGGACACGGAACTCTTGAGCGGGACGGCGTTTTCTGTCTCTTGTCTGACGATCACGGGGCATCCTG
GAGGTATGGTAGTGGGGTTAGTGGGATACCCTATGGCCAGCCTAAACAGGAGAACGATTTTAATCCGG
ACGAGTGCCAGCCTTATGAACTTCCCGACGGCTCAGTGGTCATAAATGCGCGCAATCAAAATAACTAT
CACTGCCACTGTAGGATTGTGTTGCGGAGTTACGATGCTTGTGATACACTGCGACCGCGAGATGTGAC
ATTCGACCCAGAATTGGTGGACCCCGTAGTAGCGGCGGGGGCCGTGGTCACAAGTTCAGGGATAGTTT
TTTTCAGTAACCCTGCTCATCCCGAGTTTAGAGTGAATCTCACTCTTCGGTGGTCTTTTTCCAATGGG
ACCAGTTGGAGAAAAGAAACGGTACAACTCTGGCCTGGACCGTCCGGTTATTCTAGTCTCGCGACGTT
GGAGGGGTCAATGGACGGAGAGGAGCAGGCCCCGCAACTCTACGTCCTGTACGAGAAGGGGCGGAACC
ATTACACCGAGTCAATAAGTGTCGCTAAAATCTCCGTTTACGGCACATTGGATTACAAGGACGACGAT
GACAAGTA
The SUMF1 protein sequence is:
(SEQ ID NO: 26)
MVPIPAGVFTMGTDDPQIKQDGEAPARRVTIDAFYMDAYEVSNTEFEK
FVNSTGYLTEAEKFGDSEVEEGMLSEQVKTNIQQAVAAAPWWLPVKGA
NWRHPEGPDSTILHRPDHPVLHVSWNDAVAYCTWAGKRLPTEAEWEYS
CRGGLHNRLFPWGNKLQPKGQHYANIWQGEFPVTNTGEDGFQGTAPVD
AFPPNGYGLYNIVGNAWEWTSDWWTVHHSVEETLNPKGPPSGKDRVKK
GGSYMCHRSYCYRYRCAARSQNTPDSSASNLGFRCAADRLPTMDDYKD
DDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SUMF1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
SUMF1-DNA (SEQ ID NO: 27)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGATAGCTGGACCAGGAATCAAAGAAGTTCAG
GTCTCTGAAGCGCAGCTGACACAGCATGTGCTGAGACTGATATTTGAAGGAGGCGAACAAAGATTACC
GTTGACCTAGACCTTGACTATATATTATGCACAGTAAATACATACAACCTTGGTTAAGGCATTGACCT
TTTAGCTTCATCAATTTTGAAATGAGTATAGTAATAATACATTTCTTGCCAAGTGGTTGTAATCTCAA
ATGAGAAAATGTGTGAAAGGCCTTGGCAAACTGTAAAATAGTCAACAAGGAGAAAAGGCCTTTTTTTT
TTTTTTGAGAGATGGTCTCACTTTGTCACCCAGGCTGGAGTGCAGTGGCACAATCATGGCTCACTGCA
GCCTCTGCCTACCAGGCTCAAGTGATCCTCCTGCCTCAGCCTCCGAAGTAGCCAGGACCACCGGTGTG
CGTCACCATGGCCAGTTAATTTTCTTAATTTTTTGTAGAGACAAGGTCTTGCTGTGTTGCCCAGGCTG
GTCTCAAGCTCCTGGCCTCTAGCGATTCTCCTGCCTCGGCCTCCTAAAGTGCTGGGATTACAGGCTTG
AGACACGGTGCCTGGCTGGTCTTTTCTTTATGCTAAAAAAATTCAAACAGATGCTACATTAGAATAGT
GCAATAAACACCCAGATGCCCATCAACCAGCTATGACAGTTATCAACTCATGGCCAATCATGCTTCAT
CTTTAGCCAGACCCTGATTACCCATTTTTTGGGAAGCAAATCTTTGACTGCCTATATTTTTATCCATA
TATATATATGTGTGTGTGTGTGTGTGTGTGTGTGTATACCTCAGTGAGTGTGTGTGTACCTCAGTGAG
GGGATTCTTTTAAAAAATATAGCCACAAATACCATTATTACTCCTAAAAGCCTAAAAACAAAATTTAC
AGCAATTCCTTAATTTTATCAAATATTATAATTTGACTTAGTGGTTAAATTTCCCTGATTATCTCAAA
AATTTTGAACTCAGTAGGTTTGAATTAGTATTTAGATAAGGTTCACATATTGCAGCTGGCTGCTATGT
TTTTTTTTTTTTTTTTTTTTTCAGATGGAGTCTTGCTCTGTCCCCAGGCTGGAGTGCGGTGGCGCCAT
CTCGGCTCACTGCAAGCTCCACCTCCCGGATTCATGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTG
GGACTACAGGCGCGTGCCACCACGCCGGGCTAATTTTTTGTATTTTTTAGTAGAGATGGGGTTTCACC
GTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCACCCGCCTCGGCCTCCCAAAGTGCTGG
GATTACAGGCTTGAGCCACCGCGCCCGGCCTGCTATGTTGTTTTTTAATCTGTAAGTTTCTCCTTCAT
CTTCTTTTTGTTTTGGTTTTGCATTTTGTTCGATTACGGAACTGTAGAACAGTGGTTCTTAAACTTAA
GTGTGGATTAGAATCATCTGGAGAGCTTGTGAAACCCTGGATTGCTGTGTCCAGTCCCCACGGATTCT
GATTCCGTATTGTATTTCTCTTTTTTTTTTGAGACGGAGTCTTGCTCTGTCGCCGAGGCTGGAGTGCA
GTGGCGGGATCTGGGCTCACTGAAACCTCCGCCTCCCAGGTTCAAACGATTCTCCTGCCTTGGCCTCC
CGACTAGCTGGGACTACAAGCGCGCCATTACTGGGTCTTTGTGAGGATTAAATGAGATTTTAAAAAGT
GAAGTGCTTAGCATAGTACTCTGGCACTTACCAAATGCCCAGCAAATTTGACTGTTATTTTTCAACCA
AGAAATCATAAAGGGGTGCACGGTCTGTGGAAGGCCTTGAGTTTTGTGGAGTTTTGTGTTTTGCTGCG
TTTTGACGTTAGCACAGGCAAGCAGCAGCGCCAAAGAAGTACCTGAAGAAAGGTGAAGAGCAACTCTC
CTGGTCACTTCGTAAGTCAGCTCAAAATTCTGCCCCTTTAAGGAGGGCTCAG
ATGGTTCCAATCCCCGCCGGGGTGTTCACCATGGGGACGGACGACCCACAGAT
TAAGCAGGATGGCGAAGCTCCAGCGAGAAGAGTCACCATAGACGCTTTTTACATGGATGCTTACGAAG
TGTCTAACACGGAGTTTGAAAAATTTGTTAATAGCACAGGTTATTTGACGGAGGCGGAGAAGTTCGGT
GACAGCTTTGTCTTCGAGGGCATGCTTTCTGAACAGGTGAAGACTAACATTCAGCAGGCAGTTGCAGC
GGCACCTTGGTGGCTCCCAGTTAAGGGGGCAAATTGGCGACACCCAGAGGGACCAGACTCTACTATAT
TGCACCGGCCTGACCACCCGGTTCTTCACGTATCCTGGAATGACGCCGTTGCCTACTGCACCTGGGCA
GGAAAACGACTGCCGACCGAAGCAGAGTGGGAGTATTCTTGTAGAGGAGGACTGCATAATCGGCTTTT
TCCCTGGGGTAACAAGCTTCAGCCCAAAGGCCAACACTATGCTAACATCTGGCAAGGGGAATTTCCCG
TCACGAACACTGGGGAGGACGGATTTCAGGGGACCGCACCTGTAGATGCGTTTCCCCCCAACGGGTAT
GGTCTCTACAACATCGTCGGTAATGCCTGGGAATGGACCAGCGACTGGTGGACGGTGCACCATTCTGT
TGAAGAAACATTGAATCCCAAAGGGCCACCAAGCGGAAAGGATCGAGTGAAGAAAGGCGGATCTTATA
TGTGTCATCGGTCCTACTGCTACCGGTATCGGTGTGCTGCTCGCTCTCAGAATACACCCGACTCAAGC
GCAAGCAATCTTGGTTTCCGGTGTGCGGCCGATCGCTTGCCGACAATGGATGACTACAAGGACGATGA
CGACAAATA
The GAT1 protein sequence is:
(SEQ ID NO: 28)
MATNGSKVADGQISTEVSEAPVANDKPKTLVVKVQKKAADLPDRDTWKG
RFDFLMSCVGYAIGLGNVWRFPYLCGKNGGGAFLIPYFLTLIFAGVPLF
LLECSLGQYTSIGGLGVWKLAPMFKGVGLAAAVLSFWLNIYYIVIISWA
IYYLYNSFTTTLPWKQCDNPWNTDRCFSNYSMVNTTNMTSAVVEFWERN
MHQMTDGLDKPGQIRWPLAITLAIAWILVYFCIWKGVGWTGKVVYFSAT
YPYIMLIILFFRGVTLPGAKEGILFYITPNFRKLSDSEVWLDAATQIFF
SYGLGLGSLIALGSYNSFHNNVYRDSIIVCCINSCTSMFAGFVIFSIVG
FMAHVTKRSIADVAASGPGLAFLAYPEAVTQLPISPLWAILFFSMLLML
GIDSQFCTVEGFITALVDEYPRLLRNRRELFIAAVCIISYLIGLSNITQ
GGIYVFKLFDYYSASGMSLLFLVFFECVSISWFYGVNRFYDNIQEMVGS
RPCIWWKLCWSFFTPIIVAGVFIFSAVQMTPLTMGNYVFPKWGQGVGWL
MALSSMVLIPGYMAYMFLTLKGSLKQRIQVMVQPSEDIVRPENGPEQPQ
AGSSTSKEAYIDYKDDDDK
GAT1 DNA (SEQ ID NO: 29)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGAGGTCGGGTCTGCTCAAGTTCTGCAAAGAT
GGCTGCCAACACCTCTATGCTTAGGAGCTTTGGTGGAGATTGAGTTTCTGTTTGACAATAGTTTTAGC
AAAAGTCCCAGACAGAGTTCTCATTGGCCCAGCATATGTCACACGTCCCCTCATTGAGGTCAGAGTGA
TGTGCTCTGATTATCTGTGCCCTGGGTCACATGTCTGTCTCCAGGAGGAGGGAGCCCCACCCAACCAT
ATTGAATATGAGTGAAGGAGGGGAAGTTTCCCAAATGAAAATTGAGGTTCTGTCACCCAAAGAAGTTG
AAATGAATGTCAGGCAAGCAAAAGTAGCCTTCATTTTTGCTACCCTTGTATCTCCACTCAAAGCTATG
CCCCACATCTCCATCCAGACAGCTCCTACTCATCCTTCAGACCTCAGTTCAAATGGCGCTTCCTTGAG
GAAACCTTCCCAAACCATCCCACACTAGACTGGAATCCCCTGCTGGACTAGAATCCCCTGCATGTGTG
CTCCTGGCAGAGCTTGTCATTCTGGGTTTGTGCGGTTATTTGATGAAAGCCTGTCTCCCATACTGGAC
TGGCATCACCTTGAAAGCTGTGGCCTGTCTTGTCCATCGCTCTGTCCCTGGAGCCTAGGACAGTGCCT
GGCACACAGGTGGAACTCGGGAAATATTTATTTGAAATACCAACGGAAGTCCACAGCACATATGACCT
GGTGATCAGTGGTGGGAGGTGAATGGGTCAAGAAAGACACCAAGATTCCCTGCTCATGAGTGAGAGTG
TGGGGAAACAGAAGAAGTCAGGGTGACCTTGGTGAGCACTGCCCTGGGGGACTCGAGGATGGATGAAA
GCAGGGAGGAGGCCAGATTAGGTGGGGTAGAGGACCTGAGGTCCATCAGCAAAGGCCATCCCTGGGGA
CAAAGAGAGGAGGGGAAGAGTAGGTCTGGGCTGGAGAGAAGGAATCTTTTCTCTGAGTTCCTGGGGAC
CCCAGAGGGAAGGGCAGATGTGGCCCCATTCCCAGAAGCCTTTATAAAAGAGGGTGGGGAGGTCAGGC
CTTGGCAAGGACAAGGGAAGGAGTCCCTACGTGCTGGATTGGGATTGGCTGGAAAGGGGACTTCTCTG
GGAGAATCCCTCAAACCTCAAGAACTGAGAGAAGGGTGTCTGGGGCTCCTGCCACCATCCCTGTTTCC
CTTTTAAGTAATCTGTTTCCCCATCTGTCCATCCATACACACAGCCACTTGTGTCTCCATGACCAACC
GCTGGCAGTGGAAGGGTGTCCTTCCCACCCCCACTCTTACACACACTCCCAGCTGGTACCCAGAGCCT
GGTCACCCCAGGCCAGGCCTGTGTTTCCAGGTGTAACGGGCAGCAGACGCTGCCCTAGGACTAGAGCA
GGGAGGGGGCACGGGCCCACCCCAACCCACAGCGACCCACAGAGGGCGAAAAGAGGACGACCGCAGAG
AGAAACGGAAAGGACAGGCCAACGGAAGCAGTACTGCAAGGCTGGAAGGAGAAAAGCCAGGAGGGGAG
TGCTTGCTGTGAAAGACAGGGAGACAGAGACCAAGACGGACAGGCAGACAGGCTGGTGACCCAGGATG
AGGCCGGAAAGAGCCATCAAAGGAAGGAGAAGGAAGGAGAGAGATTGGAGCGGGACGGCGGGGCAGGC
GAGGGAAGGAGGGGGTGGGGAGAGGGAGGGAGGAAGAGAGGGGAGAAAGAGGGAGGAAGAGAGGGGAG
AAGGAGGGAGAAGAGAGCGGGAGAATGCGAGAGGAAAGAAGGGAGAGGGGAGGCGTAGAAGGGGAGAG
GAGGTGAAGGGAAAAGGAGAGAGCCTGCTGGCGGCGAAGCTGCAAGAGGCAGCTGCGGAGGGAGCGCG
CGGCGGGCCTGGGGGAGCGCTGGGCGGGGGCGGGCGGTGCGGGCAGGGCTATACCCGAGCTGGGCGGG
CTCCGGGCGCCGCGGGCCCTGCCCTCCCCCTCCATCCCTCCGGACTCGCTCCCCCCTCCTCTCCCTTC
CCCGCGACCCTCCGCC ATGGCAACTAACGGTAGTAA
AGTCGCGGACGGTCAGATCTCCACAGAAGTTTCTGAAGCGCCGGTCGCAAATGATAAACCAAAGACCC
TCGTAGTCAAGGTACAGAAAAAAGCTGCTGACCTTCCTGATCGAGATACCTGGAAGGGCAGGTTTGAT
TTCCTCATGTCATGCGTTGGGTACGCCATCGGCCTCGGAAACGTATGGAGGTTCCCCTACCTGTGCGG
TAAGAATGGTGGCGGAGCCTTCCTGATACCATACTTTTTGACTCTCATATTCGCAGGCGTGCCACTCT
TCTTGCTCGAGTGCAGCTTGGGCCAGTACACGTCTATAGGCGGCTTGGGCGTATGGAAGCTGGCGCCC
ATGTTCAAAGGTGTTGGCTTGGCCGCTGCTGTACTGTCCTTTTGGCTGAACATTTATTACATAGTGAT
CATATCCTGGGCAATTTACTACCTCTACAATTCTTTTACGACAACACTGCCCTGGAAGCAATGCGATA
ACCCATGGAATACGGACCGATGCTTTTCCAACTATTCAATGGTAAACACCACGAATATGACGTCTGCG
GTAGTCGAATTTTGGGAACGGAACATGCACCAGATGACCGATGGTCTCGATAAACCGGGTCAGATTAG
ATGGCCACTCGCAATAACTCTTGCCATCGCATGGATACTCGTATACTTTTGCATCTGGAAAGGTGTCG
GATGGACAGGCAAAGTAGTCTATTTTAGTGCTACATACCCTTATATCATGTTGATTATACTGTTTTTC
AGAGGAGTCACACTTCCTGGGGCGAAGGAGGGCATTCTCTTCTATATCACGCCAAACTTTCGAAAGCT
GAGTGACTCAGAGGTTTGGCTCGATGCTGCAACTCAGATATTCTTCTCATACGGCCTTGGTCTGGGTA
GTCTCATAGCCTTGGGTTCCTACAATTCCTTTCACAATAACGTGTACCGAGACAGCATTATAGTATGT
TGTATTAATTCTTGCACTTCAATGTTCGCCGGTTTCGTCATTTTCAGCATTGTCGGATTTATGGCGCA
TGTTACCAAAAGGAGCATTGCGGATGTGGCGGCTAGTGGGCCAGGACTCGCTTTCCTCGCCTACCCAG
AAGCAGTTACTCAGTTGCCGATTAGCCCACTGTGGGCTATCTTGTTCTTTTCTATGCTCCTTATGCTT
GGGATAGATTCCCAGTTTTGCACGGTAGAGGGTTTCATAACGGCACTTGTCGATGAATATCCGCGACT
CCTGAGAAATAGACGCGAACTCTTTATAGCAGCGGTATGTATAATCTCATATTTGATAGGCTTGTCAA
ACATAACACAAGGGGGAATATACGTTTTCAAATTGTTCGACTACTATAGTGCCTCCGGGATGTCACTT
CTTTTCCTGGTATTTTTCGAGTGCGTTTCAATCAGTTGGTTTTATGGCGTGAATCGATTTTATGACAA
CATTCAGGAGATGGTAGGAAGTAGACCGTGCATATGGTGGAAACTCTGTTGGTCTTTTTTCACGCCCA
TCATCGTGGCCGGCGTGTTTATATTTAGCGCAGTGCAAATGACTCCTCTCACTATGGGGAACTATGTC
TTCCCCAAATGGGGCCAAGGGGTAGGCTGGCTCATGGCGTTGAGTTCCATGGTCCTTATTCCAGGTTA
TATGGCTTACATGTTCCTGACACTGAAAGGGAGTCTGAAACAACGGATTCAGGTGATGGTTCAACCTA
GTGAAGATATTGTCAGACCTGAGAACGGTCCCGAGCAACCTCAGGCGGGAAGTAGTACCTCTAAGGAG
GCTTATATAGACTATAAAGACGACGACGATAAATA
The FIG. 4 protein sequence is:
(SEQ ID NO: 30)
MPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVII
DDRHVYTQQEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEG
YYIVLITKRRKMADIGGHAIYKVEDTNMIYIPNDSVRVTHPDEARYLRIFQN
VDLSSNFYFSYSYDLSHSLQYNLTVLRMPLEMLKSEMTQNRQESFDIEEDEG
LITQGGSGVFGICSEPYMKYVWNGELLDIIKSTVHRDWLLYIIHGFCGQSKL
LIYGRPVYVTLIARRSSKFAGTRFLKRGANCEGDVANEVETEQILCDASVMS
FTAGSYSSYVQVRGSVPLYWSQDISTMMPKPPITLDQADPFAHVAALHFDQM
FQRFGSPIIILNLVKEREKRKHERILSEELVAAVTYLNQFLPPEHTIVYIPW
DMAKYTKSKLCNVLDRLNVIAESVVKKTGFFVNRPDSYCSILRPDEKWNELG
GCVIPTGRLQTGILRTNCVDCLDRTNTAQFMVGKCALAYQLYSLGLIDKPNL
QFDTDAVRLFEELYEDHGDTLSLQYGGSQLVHRVKTYRKIAPWTQHSKDIMQ
TLSRYYSNAFSDADRQDSINLFLGVFHPTEGKPHLWELPTDFYLHHKNTMRL
LPTRRSYTYWWTPEVIKHLPLPYDEVICAVNLKKLIVKKFHKYEEEIDIHNE
FFRPYELSSFDDTFCLAMTSSARDFMPKTVGIDPSPFTVRKPDETGKSVLGN
KSNREEAVLQRKTAASAPPPPSEEAVSSSSEDDSGTDREEEGSVSQRSTPVK
MTDAGDSAKVTENVVQPMKELYGINLSDGLSEEDFSIYSRFVQLGQSQHKQD
KNSQQPCSRCSDGVIKLTPISAFSQDNIYEVQPPRVDRKSTEIFQAHIQASQ
GIMQPLGKEDSSMYREYIRNRYLDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for FIG. 4 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
FIG. 4-DNA Sequence (SEQ ID NO: 31)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTAGCAGCTGCTATTAGTGCCTCCCCCATA
TCCACTTGACATACACCTTTTCTATGCACGACCAGCCCAACTTCCAAAATGTTAGCATGTGCGACTTT
TTGCCTAAGGGCTTTCTCTGGCTGCCAGAACCTACTCTCCCTGAACACAGGGTAGACTGGAAGTTCTA
GGGCATCAATGTTCTGCCCTATCAGGCTTCATCCAATAACTGATGGAAGTTGGCGAATAAATACTCCA
GCTTCCTTGCCCCTCAAGAGGGGATAACTGAGACATGCCTCCCAGTATTCCCTAGTGAATTCAGCCCA
CAGAGAAATTTCTCTGGTAATATTTCCTTTATTAGTTTTCTTCCCCTCCCTGCTGCTGTTTCCTGGGA
TTACGTCTCATATAAACAACCTGCCTTCAAAGTTTTGTCTTAGGATCTGATTCCGGGTGAAATAAACT
AAGATAAAGTTAAAATGGAAGTGCTAAACTATAATAATTGAAAACTAGAATCCTTCAGGTATTTTAAG
AGTTGCTATCCTAGATAAAAACACTGTGCAAACATTTAACTAATATTCAGAAGAGTTGGTTTCATTAT
GAAACAGAACACAGCTAACTATTTTTCCCAGTTAAAAGATCCAAGTCCAAAATGCCAGAACGGACACG
GCCATCCTTCTAGTTCTTAATAAAAGGAGTACCAAACTACAGGGGGAAAGAAGCGCAAAATAACATAG
ACTTAAGTATTTCTTTACAATTTTTGTAATTTCTCAAATTTTAATTTACAATATGATCTTTGGTATTA
CATGAATGTTATCTGGGTATGCTATAATTCTATAATTTTTTTTTAAAGTTTCCTTACACTTAGCAGTT
GAGAAGCCCTCTAGCAGAGGTTTCTGAGGTTTAGAGGTTTCCTGGGAAACCTAGAATTGCCGCCTAAG
ATAGGATAGCTGCCTCTCCCCTACATCTTATACTCTTGCAGTAGGTGTTCAGTAAATATTTGTGGAAT
AAATACTTCAGTCGTTGAAAGGAGACGTGGTTTTAAAAAGTGGATTTACAAAGAGACCGTTTTGCAAG
AAAAGAAGCTGGTCTGGGGGTCCCCGCAGGAGGCGGGGTTCCGTGCAACAGATACCAAGATGCCTCCA
GGGCGGACCACGACCCAGCGGGCCGCCGGAAGGCTCCTTACCTGGCCGCAGCCGGACCCTCCTCAGGG
AAGCAACTGCCTCCAGGGACTCCGCGGGGCTGTCGGGCGGTTGCCGGGGAGACCTCTGGCCGCCACGC
ACCTGCTGCTTGGTGGGGCGGGGCCTCGAGAGGCGGGGCTGTAGTTCTTTGTCATTTCTTTTCCAATT
CGAAATAGTCACTTTTGTACCTAATTTGGCATTTATAATTATAATACACTCATTTTCACAACTATGGA
AGAGAGGGTACGCGCATGCCCATTTATGTCGCACACATGAAATGAAGAAACCTCATTTCAAGCGCGGC
TCCGCCACACTGCGCTAGTCTCTGTCGACAACTTCAAGTGGCTAGCCTCACGCACAAACGTGTGGCAA
AGCCACACTTTCCAGCTTTAGGTGATTTTAAAACAATTTCTTGGGCCACACAGCGTAGGTACAACATG
GATTAGAGGTGAGGGGAAAACTGACACTCAGTGAAGGACCGTCAGAGGGCCGGCTTCCAGGAAAATGG
GCCGCAGCAGGCAGGGAAAACACAAGGATCTATCCTGCAACTCGGAGAACCCTTTTCAAAAGAAGCTA
CCCAATCCCAAACCTTCCGCTTTTTTCCAAAGAGAGGGAGGAGATAAATAGACTCAATTAATCCGTCG
ACTTTTTCTCCGCCCATGTTTTCCTCCAATCCTTACCAAAGATGGTGCCCTTCGCTTCCTCTCTCGGC
AGCACGCAGGTCCCGGGAGCCTCTACCCGACCTCTCTATGATACGTCCTCCAGCCCCGCTCCCGACGT
GAGGGGCGGGGCTTGCCTGGAGGCGGGGCGCAGGGATCCGGAAACACC
ATGCCCACGGCAGCGGCTCCAATAATCTCTTCCGTTCAAAAGCTTGTTTTGTATGA
AACTCGCGCGCGGTATTTTCTTGTAGGTTCAAATAATGCGGAAACAAAGTACAGAGTACTGAAGATAG
ACAGAACTGAGCCTAAGGACCTTGTCATAATCGATGATAGACATGTTTATACGCAACAGGAAGTGCGG
GAACTCTTGGGCAGATTGGATTTGGGGAATAGAACAAAAATGGGGCAGAAAGGTAGCTCTGGGTTGTT
CCGAGCTGTCTCAGCTTTCGGCGTAGTAGGCTTTGTGAGATTTCTGGAGGGCTATTACATAGTGCTTA
TTACCAAAAGGCGCAAGATGGCGGATATAGGCGGCCATGCGATTTACAAGGTTGAGGATACAAACATG
ATATACATACCAAATGATTCAGTGCGAGTCACCCATOOTGATGAAGCTCGCTACCTGCGCATATTTCA
GAATGTCGATCTGTCTAGTAACTTCTATTTCTCCTATAGTTATGATCTTAGTCATAGTCTCCAATATA
ATCTCACCGTCCTGCGGATGCCCTTGGAGATGCTCAAATCCGAGATGACACAGAACCGACAAGAAAGC
TTCGATATTTTTGAAGACGAAGGTTTGATCACACAGGGAGGTAGCGGTGTATTCGGAATTTGTAGTGA
ACCCTATATGAAGTACGTATGGAATGGCGAGCTCCTGGACATTATAAAAAGCACGGTCCACAGAGACT
GGTTGCTTTACATCATTCATGGCTTCTGCGGCCAGTCTAAGTTGCTGATTTACGGGCGGCCTGTGTAC
GTAACTCTGATCGCAAGGCGATCTTCTAAATTTGCGGGCACCAGATTTCTCAAGCGAGGCGCCAACTG
CGAGGGAGACGTAGCTAACGAAGTTGAGACTGAACAAATTCTGTGCGACGCGTCCGTTATGAGTTTTA
CAGCAGGTTCCTACTCCTCCTATGTACAAGTACGGGGCTCAGTTCCTCTCTACTGGAGTCAAGACATT
AGCACTATGATGCCCAAACCCCCAATTACCCTCGACCAGGCCGACCCGTTCGCTCACGTTGCGGCCCT
GCATTTTGATCAAATGTTCCAACGATTCGGCAGCCCGATTATCATTCTGAATCTTGTGAAGGAGCGGG
AAAAGAGGAAGCACGAGCGGATCTTGTCTGAGGAATTGGTGGCAGCCGTGACATATCTGAACCAATTC
CTGCCACCGGAGCACACGATAGTATATATTCCTTGGGACATGGCTAAGTACACAAAATCTAAATTGTG
CAATGTGTTGGATCGCCTTAACGTGATCGCGGAAAGCGTAGTCAAGAAGACAGGTTTTTTCGTAAACA
GGCCCGATTCATACTGTTCAATTCTCCGACCTGACGAGAAATGGAACGAACTGGGGGGATGCGTGATA
CCTACTGGTCGCCTGCAGACTGGTATTCTCAGGACGAATTGTGTAGATTGCCTCGATCGGACGAATAC
AGCGCAATTTATGGTAGGGAAGTGCGCGCTGGCCTACCAGCTGTATTCACTGGGGCTGATAGACAAGC
CGAATTTGCAGTTCGACACCGATGCGGTGCGCCTCTTTGAGGAGCTCTATGAGGACCATGGAGATACA
CTCAGTCTCCAGTATGGAGGGTCACAACTCGTACATCGAGTTAAAACATACAGGAAGATCGCCCCATG
GACACAACATAGTAAAGATATTATGCAAACCTTGTCCAGATATTATTCCAACGCCTTCAGCGATGCCG
ATAGGCAAGATTCAATCAATCTCTTTCTGGGGGTGTTCCATCCCACTGAAGGTAAGCCCCACTTGTGG
GAGTTGCCTACAGATTTTTACCTTCATCATAAGAACACCATGAGACTGCTCCCAACACGGCGGTCTTA
TACGTACTGGTGGACACCTGAAGTTATTAAGCACCTCCCCCTCCCGTATGACGAGGTGATCTGCGCGG
TTAATCTCAAAAAATTGATTGTGAAGAAATTTCATAAATACGAAGAGGAAATTGATATCCATAACGAA
TTTTTTCGCCCATACGAACTGTCCTCTTTTGATGATACATTCTGTCTTGCCATGACTAGTTCTGCGAG
GGATTTTATGCCTAAAACGGTCGGAATCGACCCGAGTCCATTTACCGTTAGGAAACCTGACGAGACGG
GGAAGTCAGTATTGGGGAATAAGAGCAACCGAGAAGAGGCGGTGTTGCAGCGGAAGACCGCAGCTTCT
GCTCCTCCGCCCCCATCCGAGGAGGCTGTGAGTAGCTCTTCAGAAGACGATTCCGGCACCGACAGAGA
GGAAGAGGGATCAGTTAGTCAGAGAAGCACACCGGTGAAAATGACTGACGCGGGCGACTCCGCTAAGG
TAACTGAAAACGTCGTGCAACCAATGAAAGAGCTCTACGGTATCAACCTCAGCGACGGCCTTTCAGAA
GAGGACTTCTCTATCTACAGCAGATTTGTTCAACTCGGTCAAAGCCAACACAAGCAAGACAAAAATTC
CCAACAACCCTGCTCAAGATGCTCCGACGGCGTAATTAAACTGACTCCGATTAGCGCGTTTTCACAGG
ATAACATTTACGAAGTACAACCTCCACGAGTTGACCGGAAAAGTACGGAGATATTTCAGGCTCACATC
CAGGCCTCTCAAGGAATCATGCAACCCCTCGGAAAGGAGGATTCCTCAATGTACAGAGAATATATACG
CAATCGATATTTGGATTACAAAGATGACGACGACAAGTA
The CLN5 protein sequence is:
(SEQ ID NO: 32)
MAQEVDTAQGAEMRRGAGAARGRASWCWALALLWLAVVPGWSRVSGIPS
RRHWPVPYKRFDFRPKPDPYCQAKYTFCPTGSPIPVMEGDDDIEVFRLQ
APVWEFKYGDLLGHLKIMHDAIGFRSTLTGKNYTMEWYELFQLGNCTFP
HLRPEMDAPFWCNQGAACFFEGIDDVHWKENGTLVQVATISGNMFNQMA
WVKQDNETGIYYETWNVKASPEKGAETWFDSYDCSKFVLRTFNKLAEFG
AEFKKNIETNYTRIFLYSGEPTYLGNETSVFGPTGNKTLGLAIKRFYYP
FKPHLPTKEFLLSLLQIFDAVIVHKQFYLFYNFEYWFLPMKFPFIKITY
EEIPLPIRNKTLSGLDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN5 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
CLN5 DNA (SEQ ID NO: 33)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGCTTGGTTATGTCAGTTCCTGTGTGTAGACA
GTAAGAAAAAAAAAGCCATGCTATGTGTGACATTTTTTTCCAATGTTTATTTCCCACCAAAAAGTAAA
TGCATTTTAACCCATTCTGTGGTTCACTGTAGCTTAAGGAAACCAAGCATATAGATGCATTAGTGATT
TTGTTTATATTATGTAAAATGTAACGATCTATCTTAGAAATACCACAGTTTGTATTTTTCTTTAAGGA
GTAAAGATTTGTCTTTAAAAATAACTTGATATTTTCCTGGCTTTCATTTAATACAATGGAAAATAAAG
TATTACACGAAAAAAAAATTTTTTCTTAGAGACAGTATCTCATTATGTTACCCAGGCTGAAGTGCAGT
GGCTATTCACAGGCACGATTATAGCTCACTATAGCCTCAAAGTCCTGGGTTCAAGCCTCCTGAGTAGC
TAGAACTTCAGGTACATGCCACCTTGCCTGGCTTCCTGCTTTCTTATTCACTAAGAAACTTTGTTCTC
TAAAATCATAGATTAGAGACAACTTCGTGTTTGAAATTACATCAGTAACAATAAAATATCCCACCTTT
GCTTGAAGGACCTCAGTCATTCCACACAGAGAATTGGCCTCAATTTACAACCCAGATGTCAAGCTTCT
GATAAGGGGTTTCCAGACACAAAACTCCATCGCTATTTTAACTTCATAGTCTCCAAGGAAATAGGCCC
TTCATCCACTTTGCAGTCTAGACCTAGAGCCTGTGTGTTGATGGCAGCAGCAGGCCGTCTGGAGCAGC
CACTACCATCATTGACATACAGCCTTGTTTTGCTTTGAGTCTACCAAAATACTGCTTATTTAAATTTC
ATCTCAACTCCACACTTCCCCAGAATCCTATCACTCTATCTGGGGAGATGCCATGTGGTCCAGGCAGT
CTTAGGCTGAATGGGCAAGGATCCAAGGGAAACCAATTAGATTGAAATTAGTTCTGTCTGTGGGCCCT
CAAGATTTAAAAGCCATGGACAAGGGGGAAGCAACCAGTATCGACCAGCGATAATCTATGAGCACCTT
CAGCTTGGGGTGTGGGGTCATAGACAAAAAGAATGGGGTTTAATCAGTGTTCCCATCCAAGGCAAAAC
CAGACCAGAAGAATGGGAGCTACCAGGAGGCTGAGTTAAGACCAATACTAGGGCCAGGCATGGTGACT
ACAGCCTGTAATCCCAGCACTTTTGGAGGCCGAGGCAGGTGGATTACTTGAGGTCAGGAGTTCGAGAC
CAGCCTGGCCAACATGGTGAAACCTCGTCTCTACCAAAAAAAAAAAAAAAAATTACAACTGGCACACA
CTTGTACCCAGCCACTAGGGAGGCTGAGGCAGGAGAATTGCTTGAACCCGGGAGGCGGAGGTTGCAGT
GAGCCGAAATCACATCACTGCACTCCAGGCTGGGTGACAGAAGGAGACTCCGTCTCCAAAAAAATAAA
AAATAAAAACCAATACTAGGAAGTGCTTTCTTACCATGAAAGCTCCCTGCACACAGAATGAAGAGACA
GATGGCAGAAGCAAGACCAGAGGCCTCCACCACTGAACAAGGTCAACCTGAATTTGTTTTTGTAGCTC
TGGGAAGTCCTGAACTGAATGGGAGGTTCTACTGTGGCCCTCTACTAACAGTAGATGGAACCTGGAAC
CATCTACTGTTAATTGTCCTTTTAGTAGCCAAGACATGAAGTACCTATCTCCCTTCTTTGTATTTGGT
GAAAAGATTTGAACTCGAGCCATCTCTGCTAAAGGCATGACTTTAGTCACCCCACTGCAGTTGCTTCT
CTTTGCCTCCAAGAAAGTCCAATCTGATGGGCAGATTGTGCTTGCAGATGACTGGATTAAACTGCAAA
TATCTCATGAAGCTGCTGCCTGCATCACCGCTCTCCAGGCAGCCACGGAGGCTCTGGTTGTTGAGGCC
ATCTACTGTGGCCCTCATACATCATACTGTGTATGGTTCCAGGATTTGTAAATGCTCTAATCAATGTT
TTTTTTTTTTTTTAAAGCTGTTCCTGCTGATTGCTTTTTAAGCTAGGCTCAAGTGTGGGGCCACGGAA
TCCTTCAGGTGCCCTTCAAATCAGACATTACATTTCAGCTCTCAGGGCTAGAATGCTTCCCCCTCTTA
TCTTGGGCAGGTCTTTGAAGAAGCCAGTTTAGCCTTGGTAATTTTGAATTTGGCCATAGTATACGGAG
GAGAGCTAGGTAGCTATCAAAACGCTTAGACAAACGTATGGTAAAATGCAGCCCAGCCTGAACCTCCG
CAAAACCCCCAAACCTGGAGCAGCAAGTGGGCAAAGGAGTGTGTGTTTGGGGCAGGGTACTGAGTCCC
ATATGTAATCAAGAGACCTGGAGGGCCCAAGGAAGTCAGTGACACCCCCACAAGCTACATATCCTCCA
ATGGATTGTGGTGGTCATCTCCGGCTACCGAAGCCACCTTGCTTATTCCCATAGGCTTACAAACATTA
TGATGCTTCACACGAGTTGTGGGTGAAGTGAAGGAATTGGAAAGTCCCGGTCTAAGGCCCTGCAAAAC
TGCTGTCTGGTAAAAACAAGTGACTATGGCAAGGCCCTGAATGTACTACGTATAGACTTAAGTCAGTA
TTTGTGCCTAACAGCAAAGCATGCCACAAGAGGCTCCTCAAAAGCCGGGTAATTGATGCCATTGTTTT
CTTGACCTAGTTGAAGAGTCAAAGAAGAGAAGGTGATGCAGAAACTTCTTTCCAGTGAAGTGACAGAT
CCAAGCAAGGAACACCTGCCTGTGAGGGGAGCGGTAGGGGAGGGGGTAGATTCGGCAGCACTCGGGTA
GTGGCAGGGACCACATATTGTCGGTGTTAACCACTGTTATCACTGGCCCAGGTCGAGTGAGGACGAGT
CATTTCCCCACTAAGCACTTGGGGAGTGGCAGGGACCACATATTGTCAGTGTTAACCACTGTTATGAC
TGGCCCAGGTCGGGTGACGACGAGCCATTTCCGCACTATTGTCCCTTCTTCCTCACTGCACCCCCAGC
CCTGCACCCTCAGCTCCAAATACACATTCTCGTTCACTCAACGTTTGTTGACACCTAGCGTGGGCCCT
GTGGGATGGGGTAAAAGTTCGGTGTTGGGAGGAGCCCCGGTGACAGATTTTTGGTTTTGGTGGTGGCT
TTTGGGCAAGGACAGGTCAATTCATAAAAGATGACGCCCCAGGTCTGGATCGAATTCTCCTGGGAGCC
AGACCAAAGCACCTTCCTGGACTGCAAAGTGTGGAAGCCGCCGCGGGCCGGGCGCGGGGAGGTGTCAT
GCGCCGGAACCTGCGCTTGGGGCCAAGCTCTGGAGCTGACGCGCAGGGGCAAGGCGCCCCGCGTCCCG
GACTGGCGGCTCCGCGCATGCTCCTCCCACCGGCGTCGCAGGCCTCGAGAGGCTCCGG
ATGGCTCAGGAGGTCGATACAGGAGAAGGGGGAGAGATGGGGAGGG
GAGCGGGAGCGGCGCGAGGCAGGGCAAGCTGGTGTTGGGCACTCGCACTGCTCTGGCTGGCGGTTGTC
CCGGGATGGTCTAGAGTGAGCGGCATTCCAAGTAGGAGGCATTGGCCAGTGCCCTACAAACGATTTGA
TTTCAGACCCAAGCCAGACCCGTACTGCCAAGCAAAGTATACATTCTGCCCCACTGGCAGCCCCATCC
CTGTGATGGAGGGGGATGATGATATAGAGGTCTTTCGGCTCCAAGCCCCAGTATGGGAGTTTAAATAT
GGAGATCTCTTGGGCCATCTGAAAATTATGCACGATGCGATCGGGTTTAGATCAACATTGACAGGCAA
AAATTACACCATGGAGTGGTATGAACTCTTTCAGTTGGGAAACTGCACTTTTCCGCACCTTCGACCTG
AAATGGATGCCCCTTTTTGGTGCAATCAGGGCGCGGCTTGTTTCTTTGAGGGTATAGACGATGTACAC
TGGAAGGAGAATGGCACACTTGTACAGGTGGCAACAATCTCCGGTAATATGTTCAACCAAATGGCTAA
ATGGGTTAAACAGGATAATGAGACTGGGATATATTACGAAACCTGGAATGTAAAGGCTAGCCCAGAAA
AGGGTGCAGAGACGTGGTTTGATAGCTACGACTGCAGCAAGTTCGTCCTGCGGACCTTCAACAAATTG
GCGGAGTTTGGAGCAGAGTTTAAAAACATAGAGACTAATTACACACGCATTTTTCTTTATAGCGGCGA
GCCCACTTACCTCGGTAACGAGACATCAGTCTTCGGGCCCACCGGAAACAAGACCCTTGGTTTGGCGA
TTAAAAGATTTTATTATCCATTCAAACCTCATTTGCCAACTAAGGAATTTCTCCTCTCTCTCCTGCAG
ATATTCGATGCGGTCATTGTTCACAAGCAATTCTACTTGTTCTACAACTTCGAATATTGGTTCCTTCC
AATGAAATTCCCATTCATTAAAATCACATATGAGGAGATTCCCTTGCCCATAAGGAACAAGACTCTCT
CAGGGCTCGATTACAAAGATGATGACGACAAATA
The AGA protein sequence is:
(SEQ ID NO: 34)
MARKSNLPVLLVPFLLCQALVRCSSPLPLVVNTWPFKNATEAAWRALA
SGGSALDAVESGCAMCEREQCDGSVGFGGSPDELGETTLDAMIMDGTT
MDVGAVGDLRRIKNAIGVARKVLEHTTHTLLVGESATTFAQSMGFINE
DLSTTASQALHSDWLARNCQPNYWRNVIPDPSKYCGPYKPPGILKQDI
PIHKETEDDRGHDTIGMVVIHKTGHIAAGTSTNGIKFKIHGRVGDSPI
PGAGAYADDTAGAAAATGNGDILMRFLPSYQAVEYMRRGEDPTIACQK
VISRIQKHFPEFFGAVICANVTGSYGAACNKLSTFTQFSFMVYNSEKN
QPTEEKVDCIDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for AGA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
AGA-DNA (SEQ ID NO: 35)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG6
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTGTCTCTACTTAAAATACAAAAATTAGCCG
GGCATGGTAGTAGGCAGTAGCAATCCCAGCTACTCAGGAGGCTGGGGCAAGAGAATCGCTTGAATGCA
GGAGGTGGAGGTTGCAGTGAGCTGAGATTACACCAGTGAACTCCAGCCTGGGCGATAGAGCAAGACTC
CATCTCAAAAAATAAATACATACATACATACATACATACAAATATCCATGGAAAAGTTGATATATTGA
GACCTTCTATCAGCCATTCCCACTATAGTGTAATTTAGCTGTTTCTCTGACAGGAATTTTTATTTAAG
AAGAAAGAATTTGGAGAAATAGACATAGTAGGAGGTAACAGATCAGGCTCTTTCCACCAGAAGAAACA
CAAATACCTTAAAAAACAGGAAGAGGCTAGAGAGATCAGTGGGGTACTAAGACCAATTTTCCATGTAT
TGTATTTTACAATTTTTGCTAAAGGCATGTCCTAATTCCTTAAGGCTGCATAAAAATACTCAGCCCAG
GAGCTAAGGAAAATTTACTCAGAGGACAATGTATGTTTTTCTGGCTTTCTTACCCTGTTTCACCCAAG
TTTCCAGTTTCACCTGCCATTGGGTTATGATTACTCCAGCACAGATGACTTGTTCCTCTTCCAAACCC
CATGAAAGGAACTTAGAAAATTTGTCTTTATTATATCTTTTAATTAACACTTCCCCAACGGGATAATG
ATACTTCTGGGCTATCTTATGTTCTTTAAATTATGTATTTAATTTCCTAGCAATCAATAAGAGCCTTG
AAGGTTTTGTAAGTCTCACAACTCCTACCTAGTTTATATTTTTACATTTATTTATTTATTTATTTTTG
AGACAGAATCTCACTCTGTTGTCCAGGCTGGAGTGAAGTGGTGCGATCTCGGCTCACCACAATCTCCA
CCTCCCGGCTTCAAGCAATTCTGCCTCAGCCTCCCAAGTAGTTGGGACTACAGGCATGCACCACCACG
CCCGGCTAATTTTTGTATTTTTAGTAGAGACGGGTTTCACTATGTTGGCCAGGCTGGTCTCGAACTCC
TGACCTCGTGATCCACCCACCTCAGCATCCCAAAGTGTTGGGATTACAGGCGTGAGCCATCGTGCCCA
GCCTAGTTCATATTTTTAAAGTTTGTATAGATTTATAGATGCTTTTAAAAATTATGTGATTATGTGTC
TTGCCTTGGCAACCTGGGCAGGCATTCCAGACACCCAAAGGGATTATTAGTTCATGTTCGCACGTCTG
CCCAGCAACAAAACTGAGCAGCCTCCACCAAGCACGTAAAATCCCCATTCCTCCTCTTATTCATTTAT
TTAGCACTTAATAGTGCCAGGCAGGAAGGTAAAAATACATTTAAAAAGGAATGGAGGTAGCCGTCTTG
CCCTGGAGGTGCAGGAAGCTGCACTTCAGTGTGCTAGGTAGAGGGTACATAGGCCGTTTCTGTTTTTC
TTCCAGCTCAGGGATTTATAATGAGAGGAAGTGCTACAAAAAGCTGTGGTGCGAAAATGACGGACGCT
ATGAATGGAAAAAAAATCTAAAATCAATCCGGTCCTAAGCAAACACGCTTCACCTACACTCATAACTA
TTGCAGACCTCCGAGGCCTGGGATCCCCAAGAATATACTGAGTTTGACAAACTTTTCAACTTCAACTT
TAAATTAAAAAGACAGTAAAAGAACCAAATCCATAGTACACAGCAATCGGCTAAAGTTCCTGGGGCCC
TGCAACCCAGAGTTGAATAATTTTGTATTAAATTCCCAATATCAAGCTAAATCTATTTTAACCACAGG
AAAAGCAGCAACTTGTCTGGCTATTTTAAAAATCTGAACAGCACTTAGGAAGAAGCACCTTAGCGCAG
GGAACAGCTCAGTGCCCCGTGACACAACTCTCCCGCGGGCCCAGGGACGCCTCGTCTCGCGAGAGTTG
AGGGACGCCTGAGCGAACCCCCGAGAGAGCGGGCGTGGGCGCCAGGCGGGCGGGGCACTGGGGAT
ATGGCCCGCAAAAGTAACCTTCCCGTTCTCCTGGTACCG
TTCTTGTTGTGTCAAGCACTTGTACGCTGCTCTTCACCGCTCCCGCTTGTCGTTAACACCTGGCCTTT
CAAGAATGCAACAGAGGCGGCATGGCGAGCACTCGCATCTGGCGGGTCTGCCCTCGATGCAGTAGAGT
CCGGCTGTGCCATGTGCGAAAGGGAACAGTGTGACGGGAGTGTGGGATTTGGCGGCTCTCCAGATGAG
TTGGGAGAAACGACCCTTGATGCGATGATTATGGATGGAACAACCATGGATGTGGGGGCGGTCGGTGA
CCTCCGCAGGATAAAAAATGCTATTGGGGTGGCGAGGAAAGTCCTGGAACACACCACCCATACTTTGC
TCGTTGGTGAGTCTGCAACAACGTTCGCGCAAAGCATGGGCTTTATAAATGAGGACCTGTCCACAACT
GCCTCTCAGGCTTTGCACTCTGACTGGTTGGCGAGGAATTGCCAACCCAATTACTGGAGAAATGTTAT
TCCCGATCCATCCAAGTATTGCGGGCCTTATAAGCCACCGGGAATCCTTAAACAAGATATACCTATTC
ATAAGGAAACCGAGGATGACCGGGGACATGATACGATCGGAATGGTAGTGATCCACAAGACAGGGCAT
ATTGCGGCGGGGACCAGCACAAATGGTATCAAATTCAAAATTCACGGTCGAGTCGGTGACTCCCCCAT
ACCTGGTGCCGGGGCTTATGCTGACGACACAGCTGGAGCTGCTGCCGCGACAGGTAATGGTGATATCC
TGATGCGGTTTCTCCCATCATACCAGGCTGTCGAATATATGAGACGGGGTGAGGACCCCACTATAGCC
TGTCAAAAGGTTATTTCTCGGATACAGAAGCATTTTCCGGAGTTTTTCGGTGCAGTTATCTGCGCCAA
CGTTACTGGTAGCTATGGAGCTGCATGTAACAAGTTGAGTACGTTTACCCAATTTTCATTCATGGTTT
ATAACTCCGAGAAAAATCAGCCGACTGAGGAAAAGGTTGACTGTATTGACTACAAAGACGACGACGAT
AAATA
The IDUA protein sequence is:
(SEQ ID NO: 36)
MRPLRPRAALLALLASLLAAPPVAPAEAPHLVHVDAARALWPLRRFWRST
GFCPPLPHSQADQYVLSWDQQLNLAYVGAVPHRGIKQVRTHWLLELVTTR
GSTGRGLSYNFTHLDGYLDLLRENQLLPGFELMGSASGHFTDFEDKQQVF
EWKDLVSSLARRYIGRYGLAHVSKWNFETWNEPDHHDFDNVSMTMQGFLN
YYDACSEGLRAASPALRLGGPGDSFHTPPRSPLSWGLLRHCHDGTNFFTG
EAGVRLDYISLHRKGARSSISILEQEKVVAQQIRQLFPKFADTPIYNDEA
DPLVGWSLPQPWRADVTYAAMVVKVIAQHQNLLLANTTSAFPYALLSNDN
AFLSYHPHPFAQRTLTARFQVNNTRPPHVQLLRKPVLTAMGLLALLDEEQ
LWAEVSQAGTVLDSNHTVGVLASAHRPQGPADAWRAAVLIYASDDTRAHP
NRSVAVTLRLRGVPPGPGLVYVTRYLDNGLCSPDGEWRRLGRPVFPTAEQ
FRRMRAAEDPVAAAPRPLPAGGRLTLRPALRLPSLLLVHVCARPEKPPGQ
VTRLRALPLTQGQLVLVWSDEHVGSKCLWTYEIQFSQDGKAYTPVSRKPS
TFNLFVFSPDTGAVSGSYRVRALDYWARPGPFSDPVPYLEVPVPRGPPSP
GNPDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for IDUA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
IDUA-DNA (SEQ ID NO: 37)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTCCAGGGAAGGTGTACTTTTCTGTCCACAG
GTGTCCCGGTGAGCGGCTCACCTTAATTCTCTCAGGGCTTGAGGTGATTTAAGGCTGGCTTCAGTCCC
CACAAAGACAATTCTGTTGCTGGTTTACCTTTGCTTTTAGGGGATAGAACTTTGGGGTCCCAAGAAAA
ACCCAAAGTCTTTACCAGGCCCCCCGCCTGAGCCTCGACTTCTGTCCTGTGGCCACAGTGTGAGGAAC
GAACGCAGCAGCGTGTCGCCATGTCTTGTGTGGCTGGGATACGCTGCAGGGGTGTGGAGTCGCCGCCC
CAAAGCGGGCCCCGCCCCCTCCCGGCTTGTCCCTGCAGAGCCCCGAGGCCTCAGAGGCTCCTCAGAGC
TCCCAGTGCCCTGGACGGTTCCGTTCAGCGCTCTCCAGTTCTGATGGTTGCTCTCAGGAGGCGGCTGG
TCTGAAACAATTCAGTTTCCATTGCTGTGTCCTGCACCACGGTGTGGGACTGGTGGTTTCTTACTGTT
TTTCTCAGTTCTCTGACGCTTTGAGGAATTGTTTTTAAAGCGAGTTATCCATCATTTTAGTTGTTTTC
TCTGGGGTCGTTGGACTGAGGGTCTTACCCCGCTGTTCCTGGAGACAGTTCTGTACTTGCATGGTTTC
TCTCGCCTTTCCCTCCCTTTCTTACTTTTTAGTTTCTTAATGAATTTTTTTGTATTATGTTTTTCCTC
CTTGCTAATTTGGAATATATACACACTATTTCACTTTTAAATGGCTAATCACTTTTAATGCAATTTCA
ACATAAGAAGACCTAATGTTAAGCAATATTTTAACCCCTCTCCCCAAAATAAAAAGACCCAGAACACT
GTAACTCTAATTATCCTTCTCCCAACTTAGAGAGGATTATTGTCCAGTATTTTCGTTTTGTTAGTAGA
CTGTTCTTTTTTTCTTTTCTTTTTTTAGAGATGGGGTCTCATTTTGTCAACCAGGCTGGAATGTAGTG
GTGTGATCATGGCCCGTCTCAGCCTTGAACTCCTAAGCTCAAGCAATCTCCCACCTCAATTTCGTGGG
TAGCTGGGCCTCACAGGCATATACCATCGCATCTGGCTAAATTTTTTTTTTGTACAGATGGGGTCTTG
GTACATCTCCCAGGCCGATTTCAAACTCCAGGCCTCAAGTGATCCTCCCGTGTTGGCCTGCAATTCCA
AAGTGCTGGGATTGCAGGTGTGAGCCACCGCACCAAGCCTGTTCTTTCCATTATTATTTTTATACAAT
GTTTGCTTGGATTCACACATGCATACATGGACTACACATGTACTACAGTTGTCCCATGGTATCCTCGG
GGTATTGGTTCCAGGACCCTCCCAGATACCAAAATTTGCAGGTGCTCAAGTACTTGATATAAAATGGC
ACAGTATTTGCACATTACCTACGCACATCCTACTGTGTAGTTTAAATCAAGATTACTTATAGTCCCTA
AAACAATGTAAATGCTCTGTAAATAGCTGTTATACTGTATTGTTTTAAAATATGTATTATTTCGTATT
GCTTTGGCTTTAAAACAATATTTTCAGTCTGCTTGGTTGAATCCATGGATCTGAAGCCAAGTGTAAGG
AGGGCCCAGTGTGCTCTTCTGGGGTAATTCTCCTTCCTGCTAAAGCGCACGCTTTACTCAGGAGGCTG
GGGTGAGAAAATCGCTGAAGCCCCGGAGATGGAGGTTGCAGTGAGCTGAGATCGCGCCACTGCACCTC
AGCCTGGGCGACAAAGCAAGACTCTGTCTCAAAAACACACAAAAACAGAGAAAAACAAGACAGTAATG
GCTCAACTCACATAGCACCAACGGGCGAAGCGTTCTTCTGAGCGCTTTCCGAGTCATCGGTCCTCAGA
GCAGCCCCTGAGGCCCGCAAGGAAGCGGGGCTCCAAGCCCTGCCGTGCTCCCGGCTCCCCGAGGCTCC
CCGAGGCCACCCAACCCCTCCCACCCGGCCATCGCCCCCTCACCAAGGCCCCGCCCCGCGGCGGCGGT
CACATGGGGTGCGCGCCCAGACTCCGACCCGGAGGCGGAACCGG
ATGAGGCCACTGAGGCCAAGAGCTGCACTTCTGGCGCTCTTGGCGAGTCTTCTCGCCGCA
CCTCCCGTTGCCCCTGCGGAGGCACCACATCTCGTTCATGTTGACGCTGCGAGGGCTTTGTGGCCACT
TAGGCGATTCTGGAGAAGTACGGGCTTCTGTCCACCGCTGCCGCACTCACAGGCAGACCAATATGTCT
TGAGCTGGGATCAGCAACTCAACTTGGCGTATGTGGGAGCTGTCCCGCATCGCGGTATTAAGCAAGTG
CGAACGCATTGGTTGCTTGAGTTGGTAACCACGAGAGGTTCCACTGGGCGAGGGCTCTCCTATAACTT
CACACACCTCGATGGGTATCTGGACCTGCTGCGAGAAAATCAACTCCTTCCCGGGTTCGAACTGATGG
GCTCCGCATCTGGCCACTTCACGGACTTCGAAGATAAGCAGCAGGTCTTCGAATGGAAAGATCTGGTG
TCAAGTCTGGCTCGCAGGTATATTGGACGATACGGTCTGGCCCACGTCAGTAAGTGGAATTTTGAAAC
GTGGAACGAACCAGACCACCATGACTTTGATAACGTATCTATGACTATGCAGGGATTTCTCAATTACT
ATGACGCTTGCTCTGAAGGACTCCGGGCTGCAAGTCCAGCTCTCCGCTTGGGCGGGCCTGGGGATAGT
TTCCATACACCTCCCCGATCCCCGTTGAGTTGGGGGCTCCTCCGACATTGTCACGACGGGACGAACTT
TTTCACCGGTGAAGCGGGAGTTCGGCTCGATTACATCTCTCTGCATCGGAAGGGCGCAAGAAGCTCCA
TAAGTATCTTGGAGCAAGAGAAAGTCGTGGCGCAGCAGATCAGACAGCTCTTCCCGAAGTTTGCGGAT
ACACCTATATACAATGATGAGGCTGACCCACTGGTCGGCTGGAGCCTGCCCCAGCCGTGGAGGGCTGA
CGTAACATACGCCGCGATGGTGGTTAAGGTAATAGCCCAGCACCAGAATCTTCTGTTGGCAAATACCA
CGAGTGCATTCCCTTATGCTCTGTTGTCAAATGATAATGCCTTCTTGTCTTACCACCCGCATCCTTTC
GCTCAACGCACGCTGACCGCCCGCTTTCAAGTAAATAACACTCGCCCACCCCACGTGCAGCTCCTGAG
GAAGCCCGTTCTGACTGCTATGGGGCTCCTCGCGCTGCTGGATGAGGAGCAGTTGTGGGCTGAGGTAT
CTCAAGCCGGGACTGTATTGGACTCCAATCACACTGTGGGGGTTCTTGCTAGCGCGCACCGCCCTCAA
GGACCTGCCGACGCCTGGCGCGCTGCAGTGTTGATATATGCCAGTGATGATACGCGAGCCCACCCGAA
TAGGTCTGTTGCCGTGACGTTGCGCCTCAGAGGCGTTCCCCCTGGTCCAGGACTCGTCTATGTTACTC
GATATTTGGATAACGGCCTCTGTTCCCCTGACGGTGAATGGCGGAGATTGGGGAGACCTGTGTTTCCG
ACAGCGGAGCAGTTCCGGCGCATGCGAGCGGCAGAAGACCCTGTTGCAGCTGCTCCACGACCGCTCCC
TGCAGGCGGCAGGCTTACTTTGAGACCAGCTTTGAGGTTGCCGAGCCTCCTGTTGGTCCATGTATGCG
CGCGGCCAGAGAAGCCACCCGGGCAAGTAACCCGGCTTCGCGCCCTCCCGCTCACCCAAGGCCAGCTC
GTGCTTGTATGGAGCGACGAGCATGTTGGATCTAAGTGTTTGTGGACTTACGAGATACAATTTAGCCA
GGATGGAAAGGCGTATACCCCTGTGAGTCGGAAGCCTTCTACATTCAACCTCTTCGTGTTCAGCCCCG
ACACAGGTGCTGTTAGCGGGTCCTATCGGGTGCGGGCGCTGGATTACTGGGCACGGCCCGGGCCGTTT
TCCGACCCTGTTCCCTACCTGGAAGTTCCCGTTCCGCGAGGCCCACCTAGCCCTGGGAATCCAGACTA
TAAGGACGACGACGATAAATA
The GDNF protein sequence is:
(SEQ ID NO: 38)
MKLWDVVAVCLVLLHTASAFPLPAGKRPPEAPAEDRSLGRRRAPFALS
SDSNMPEDYPDQFDDVMDFIQATIKRLKRSPDKQMAVLPRRERNRQAA
AANPENSRGKGRRGQRGKNRGCVLTAIHLNVTDLGLGYETKEELIFRY
CSGSCDAAETTYDKILKNLSRNRRLVSDKVGQACCRPIAFDDDLSFLD
DNLVYHILRKHSAKRCGCIDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GDNF and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
GDNF-DNA (SEQ ID NO: 39)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGAAACCCTCTTAAGACGGAAGGGAAATCTAG
TGCCTCTGTGGCTTCCTGCTGGCGGGCACCGCGATTTGGAATGGCGCATTAACCCCGCGCCTCCATGC
TCCTCCGGTCGGACCGCCAGCCATTTCGCACGCACCCGGGAGCTGGCACCGGCGGGGGGCTTGAGGGG
GGAAGCTCGCGTTCCCCAGGTCCTAGCTGCCAAAGTACCTTTCTGGGCTCATTTTGCATGGCCTGGTG
CAGTTTTCCTGTGTCTGCACATCGCGACCCAGAACCTAGCTTTTTCCCGAGTTTGCAAACCAGCCCGC
GAGGCAAGAGGCGCTCGGTGCTGCAGGTCACTAGGAGTTTCTAGTCCCTACACCCTCTCGAGCCCAAC
AGCTGCATAGCGAACAAACAGACGCTCAGGAGATGTAAAATGCATTAGTCTCTGCAGAGGTGGGAGGT
GGCGGCCGAATTAAAGGCTTCCCCGGGTTGCCTGCACCGGGACAGGGAGTGGGGTTCCGGGTAGAGAT
GAGGACTGGAACCCTGGAATGGAGGCGGGGGTGCCTGTGAACTAATGGCTAGGAAAGGCACTGAGGTT
TTTGCATTAACCTGGGTTTTGCATTTCCCTCCCGCATGGGAAAAAAAAAATCGAGTTTTTCCTAAGAA
CCGTTTTATGGAGCCGGTCGAGGGGATAGGATAATCGACTGCACGAATCTCGCAGATTCCGCTTGAGG
AGATTCTCTCTAGGTCACTAGTGCCCTGGAGACGAACCCTGGGATTAGGAAGGCACTGGATAACACTG
CACCCCAAGATGCCTCGGTTCTTCCCCGTCTCCTCATTGGTTGGAACTCGCCCCCAAATTTACAGCCC
CTTTTTCTAACCCACCCCCAGCTGCGTGGCCCTCCTTTGTAGGGGTGTGAGGATTGAGAAGCCAAACA
GAGCCCACCTCGGGCTGAAAAGAGCTGAACCCCCTACTCTGCGCCGTACCACGGTCTAGGCCTTCCAG
TGCCAGAGCACC ATGAAGCTCTGGGATGTCGTGGCG
GTGTGTCTTGTCCTTCTCCATACTGCGAGTGCGTTTCCACTGCCAGCTGGGAAAAGACCCCCAGAGGC
CCCTGCAGAAGACCGATCTCTTGGGAGGAGGAGAGCACCGTTCGCTCTGAGCAGCGACAGTAATATGC
CGGAGGATTATCCCGATCAGTTCGACGACGTAATGGATTTTATCCAGGCAACGATAAAGCGGCTGAAA
CGGAGTCCGGACAAACAAATGGCAGTGCTCCCGCGCCGGGAACGAAATAGACAGGCCGCCGCGGCAAA
TCCGGAAAATAGTAGGGGCAAAGGAAGACGGGGGCAGAGAGGCAAAAACAGGGGCTGTGTATTGACTG
CCATTCATTTGAACGTAACGGACCTGGGGCTTGGTTACGAGACTAAAGAAGAACTGATATTTAGATAC
TGCAGTGGATCTTGCGATGCCGCTGAAACCACCTATGACAAGATTTTGAAGAATCTTTCTCGAAACAG
AAGACTGGTTTCTGATAAGGTTGGTCAGGCGTGTTGCCGACCCATCGCGTTTGACGACGACCTTAGTT
TTCTCGACGATAATCTTGTCTATCATATCCTTCGCAAGCACTCCGCTAAGAGGTGCGGATGCATTGAT
TACAAAGATGATGATGACAAGTA
The GLB 1 protein sequence is:
(SEQ ID NO: 40)
MPGFLVRILPLLLVLLLLGPTRGLRNATQRMFEIDYSRDSFLKDGQPFR
YISGSIHYSRVPREYWKDRLLKMKMAGLNAIQTYVPWNFHEPWPGQYQF
SEDHDVEYFLRLAHELGLLVILRPGPYICAEWEMGGLPAWLLEKESILL
RSSDPDYLAAVDKWLGVLLPKMKPLLYQNGGPVITVQVENEYGSYFACD
FDYLRFLQKRFRHHLGDDVVLFTTDGAHKTFLKCGALQGLYTTVDFGTG
SNITDAFLSQRKCEPKGPLINSEFYTGWLDHWGQPHSTIKTEAVASSLY
DILARGASVNLYMFIGGTNFAYWNGANSPYAAQPTSYDYDAPLSEAGDL
TEKYFALRNIIQKFEKVPEGPIPPSTPKFAYGKVTLEKLKTVGAALDIL
CPSGPIKSLYPLTFIQVKQHYGFVLYRTTLPQDCSNPAPLSSPLNGVHD
RAYVAVDGIPQGVLERNNVITLNITGKAGATLDLLVENMGRVNYGAYIN
DFKGLVSNLTLSSNILTDWTIFPLDTEDAVCSHLGGWGHRDSGHHDEAW
AHNSSNYTLPAFYMGNFSIPSGIPDLPQDTFIQFPGWTKGQVWINGFNL
GRYWPARGPQLTLFVPQHILMTSAPNTITVLELEWAPCSSDDPELCAVT
FVDRPVIGSSVTYDHPSKPVEKRLMPPPPQKNKDSWLDHVDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GLB1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
GLB1-DNA (SEQ ID NO: 41)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGAATCAATACACTAATACAAAACTATTATTT
AATATTTAGACCGTGTACCATTATCAAAATCAGAAAGTTAACATTGATGCGGCCGGGCACAGTGGCTC
ATGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGCAAATCACTTGAGGTCAAGAGCTCCAGACC
AGCCTGGCTAACATGGTGATACCCCATCTCTACTAAAAATACAAAAATTAGCCAAGCCTAGTGGTGGG
TGCCTGTAATCCCAGCTACTTTGGAGGCTGAGGTGGGAGAATCACTTGAACCTGGGAGGCGGAGGTTG
CAGTGAGCCGAGATTGTGCCACTGCACTCCAGCCTGGGTGACAGAGTGAGACTCTGTCCCCCCACCCC
CCCAAAAAGGAAATTAACATTGATGCATGGTACTAATCTAACCTACAAGTCTAATTCTGATTTCATCA
ACTGTCCCACTAACATCCTGTATATACCAAGCTTCTTATCGTCATCATCTCTGGTAATTTCCCCAATT
ATCCAGTGAATTTGATATTATTAGCCCTGCTTTACCAACAAAGAAACTAAGCTCAGAGAGGTTAAGTA
ATTTGCCCACAGTTACACAGACAGTAAGTGGCAGAGCTGGAATTCCAACTCAAGTGTACTTCCTCCAG
AGCCCTTGTTCTTTAATACTGAACTAGAATTGCAGAGCTTGGAAAGGACTTCACAGTGCAAGGACACG
GAATTGGTACTACAGGCATGAAAAGAAGCCAGGCACGGTGGCTCATGTCTGTAATTCCAGCATTTTGG
GAGTTCCAGGCAGGTAGATTGCTTGATCCCAGAACTTCAAGACCTGCCTGGGAAACGTGGTGAGACCC
TGTCTCTACAAAAAATACAAAAATTAGCCGGGTGTGGTGGCGCACGCCTGTAGTCCCAGCCACTTGGT
AGGCTGAGACGGGAGAATTGCTTGAGCCCAGGAGGCCAAAGCTGCAGTAAGCCGTGATTGCGCCCCAC
TCCAGCCTGGGTGACAGAGTGAGACCCTGTCTCAAAAAACACAAAAACAAAACAAAAAAACAACCCCC
CAAACCAAAAAACAAAAACCTAAGAAAAGCCAGTAACTGATACTTTCTCAATCTCTCAATGAAATGTC
CTTTCTGATACTTTCTCAATCTCTCAAGGACATGTCCGGTAGGAAAGGAGAAAGGAGTGAACAAATAG
AATTTTGGCTACTTTGTTATACAATGTAAAAAGGCTTTTTGGAACACCAAGGCATAAACTAAGGTTAT
TTTAAAAAAGAAAATTTTTTTTTGATACGGAATTTCGCTCTTATTGCCCAGGCTGGAGCGCAATGGCT
CGATCTCGGTTTACTGCAACCTCCACCTCCCGGGTTCAAGCGATTCTCCTGTCTCAGCCTCCTCAGTA
GCTGGGATTACAGGCGCCTGCCACCACGCCCGGCTAATTTTTGTATTTTTAGTAGAGACGGGGTTTCA
TCATACTGGTCAGGCTGGTCTGGAACTCCTGACCTCAGGCGATCCGCCCGCCTCGGCCTCCCAAAGTG
CTGGGATTACAGGCGTGAGCAGGATTTTCATTCTAACAAGTTCCAGGTGAGTTGATACAGTGGCTCCA
GGGACCGACCACATTTTGCTAACCCCCGGCTTAGAGTTATTCAAAGAGCCCGTATATGAGACGCGGAT
TCCATCTAGGGCGTTTAGGTTTAATGATTAACAATTTCCCTCTTCTGCTCTCTCAAGGCAGCCAGGGA
ACAGGGAGACCATGATTCATGTCCAATCCCCGAGGCGCGTTATCAAGCTGCTGAAAGCAGGCCCTCCG
GACTGCAGTTCCAAAGGGTCCCTTCCCAGGGAAGACGCCTGCAAAACCCAGATAGTACTATCCTGGAG
TCACGCGGCGGCGCGCAGCCTCCTAGCCGCCCCCACCCGCCCGGCTCGG
ATGCCGGGGTTCCTGGTGAGAATACTTCCCCTGTTGCTTGTGTTGCTCCTGCTTG
GTCCCACCAGGGGTTTGAGAAACGCGACACAAAGGATGTTTGAGATTGATTATAGTAGGGACTCATTC
CTCAAAGACGGGCAACCATTCCGCTACATCTCAGGCTCCATTCATTACAGCCGAGTACCTCGCTTCTA
TTGGAAGGATCGGCTGTTGAAGATGAAAATGGCCGGGCTCAACGCGATCCAAACTTATGTCCCCTGGA
ATTTTCATGAACCGTGGCCTGGCCAGTACCAGTTCTCCGAGGACCACGATGTGGAATACTTTTTGAGA
CTTGCTCATGAGCTTGGCTTGCTTGTAATTTTGCGGCCGGGGCCTTATATATGTGCAGAGTGGGAGAT
GGGCGGACTTCCAGCGTGGCTTCTTGAAAAAGAATCAATTCTGCTCCGGAGCTCAGACCCTGATTATC
TTGCCGCTGTTGACAAATGGCTGGGGGTCTTGCTCCCTAAAATGAAACCACTCCTTTACCAGAACGGA
GGTCCGGTAATTACCGTTCAGGTTGAAAACGAATACGGTTCCTACTTCGCCTGCGACTTCGACTACCT
CCGCTTTTTGCAAAAGCGATTTCGGCACCACCTTGGAGATGACGTCGTCTTGTTTACGACTGACGGGG
CTCACAAGACATTTTTGAAGTGTGGCGCCTTGCAAGGTTTGTATACCACCGTTGACTTTGGCACCGGT
AGTAATATCACTGATGCATTTCTCTCTCAGAGAAAGTGTGAGCCAAAGGGTCCTTTGATCAATTCAGA
GTTCTATACTGGATGGCTGGACCACTGGGGACAGCCTCATAGTACGATCAAGACTGAAGCCGTCGCGT
CTAGCCTTTACGATATCCTCGCACGCGGAGCCTCCGTTAATCTGTACATGTTCATCGGTGGGACGAAC
TTTGCGTACTGGAACGGAGCAAATTCTCCGTATGCTGCACAACCCACTAGCTATGATTATGATGCTCC
TCTGAGTGAGGCGGGCGACCTTACAGAGAAATATTTCGCTCTCAGGAACATCATCCAGAAATTCGAGA
AAGTTCCAGAGGGGCCCATCCCACCTTCAACACCAAAGTTCGCCTATGGGAAAGTCACACTGGAAAAA
TTGAAAACAGTAGGAGCAGCTCTCGATATACTGTGCCCTTCCGGTCCGATAAAGTCTCTGTACCCACT
TACATTCATTCAAGTTAAACAGCATTATGGTTTTGTGTTGTACAGGACTACCCTTCCCCAAGATTGTT
CAAATCCTGCACCGTTGAGCTCACCACTTAATGGGGTGCATGATAGAGCGTATGTCGCGGTGGACGGT
ATCCCCCAAGGGGTTTTGGAGCGAAATAACGTCATTACGCTCAATATAACTGGTAAGGCTGGGGCCAC
CCTGGATTTGCTTGTAGAGAACATGGGGCGGGTTAACTATGGCGCGTACATCAACGATTTCAAGGGTC
TGGTGTCAAACCTTACGCTGAGCAGTAACATACTGACTGATTGGACTATCTTTCCTCTTGATACGGAG
GACGCTGTTTGTTCTCACCTTGGGGGCTGGGGACATCGCGACTCAGGGCATCATGATGAAGCTTGGGC
ACATAACTCCTCTAACTACACGCTCCCCGCCTTTTACATGGGCAACTTCAGTATACCAAGTGGCATCC
CCGACCTCCCTCAAGATACCTTTATTCAATTCCCAGGCTGGACAAAGGGTCAGGTCTGGATCAATGGT
TTTAATTTGGGAAGATATTGGCCAGCCCGGGGACCCCAGCTGACTTTGTTTGTGCCCCAACATATTCT
GATGACGAGCGCTCCCAACACTATAACCGTTCTCGAATTGGAGTGGGCCCCCTGTTCCAGTGACGATC
CTGAGCTCTGCGCAGTCACCTTTGTAGACAGGCCAGTCATTGGTTCCTCTGTGACTTATGACCATCCA
TCCAAGCCTGTCGAGAAGAGATTGATGCCGCCTCCTCCGCAGAAGAATAAGGATAGCTGGCTCGACCA
TGTAGACTACAAAGACGACGACGATAAGTA
The PMP22/MFN2 protein sequence is:
(SEQ ID NO: 42)
MLLLLLSIIVLHVAVLVLLFVSTIVSQWIVGNGHATDLWQNCSTSSSGN
VHHCFSSSPNEWLQSVQATMILSIIFSILSLFLFFCQLFTLTKGGRFYI
TGIFQILAGLCVMSAAAIYTVRHPEWHLNSDYSYGFAYILAWVAFPLAL
LSGVIYVILRKREDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PMP22/MFN2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
PMP22-DNA (SEQ ID NO: 43)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGGAGTTTTCCTCACCTGACTCTGGGAAGGG
AAGAGAGTCTGGCCCAGATGGGTAAAGACAAGTGTGTTGGCATCTGGTAGACAGGGCCAGTGGCACAC
AACAGTGAACAGCTCTACTGCTGACAGCCAACAGGGACTTCGGGGTTTGGCTGCTGGAGATGGAGGAC
CTGGGCAAAAGAGACGTGAGGCCAAGAGAGCAGGTCTCAGAATGTGGAGCTCATGGAAGGAGAGAGGG
AGGGCTAATCAGACTGCTCCTATCTGGCCAGAAGCCATGCCCCACACTCACCAGGCCCTACCCCTTTT
CCTCTGAATCTTTAGCTCTTAGATCAGAAATAATCTTACGTGTCTTCAGGCTTGATCCTGGCCTGACG
GACAGCAGCCTCTGTCGTGTAGCCTTTGGAGCTGATCATGGCAGTACCCAGGAAAAGACTGTCTGGAG
AGGCTGCAAAAACCATGCTCACTGTTCCCAGTCCCCGTACAGACCATGTCAGAGGAGGACTGAGGGAG
GCTCCTCTCTCTCTCTCTCTGTCACACACACGCACACGCGCACACACACACACACAGATACACGCGCA
CACACACACACCGTTTTGCCTGGCAGAACAGACTTATAACTTGCATAATACTGCAGCAGCCCACACTG
TACCTCATCTCCATTTGGGTTCCACAACAGAAGGGAGCTGGAAGGAAATCAGCGACAATCTAACTCCA
CATGACAACCTGGCTGGACAACGAAACATCCAGCGGGGAGAAAGACACTGGAAATTACCCATACCTGA
GCCCCATCCCAAAACACCTGAGTCAGCTTCTCTGACCATGGCCCAGGCTAGGTCATTTGCAAAGCTCT
TGAGTGATTCTAAAGAACCACTGCTGTGAAAAATAAAAATGATTTCAGCAAAGAGAGAAAGGTGAAAC
TATTTTATTGGCACTGGCTGTGATGCTGGCTGTGAGCAGATGCTGGCTGTGGGCAGAACAGGGGAGAG
GGCCATTGAGAGGCCCTTGTGACTGGAGAGTCCAATCAAACGTAAAGTGTGTGACAGGGAGGGACTCC
TCCAAATTCTGCAGGTCTCTCCAGACTGGGGATCCCTAACACAAGAGGAAGTCTTATGCCCCAAGTGC
CAGAATTCCAGGAAACTCATGCAATGAAACCAGTCCTCTTGTGTCAGAGTTTGCAGCTAGAAGCGGTT
CAAGGGATGGAGGACTCTCTGGGAGCTGGAGTGGTACGCTGCAAAGAACCTAAATATGCCATAACTTC
CTTTACTTCCCTCTCCAAGAATTTCCAATTGCTCTTCCAGCCTATTCTGCCTGACAGGTTAGAAAGTT
TTCAATAGTTTTCAATAGAGGTTCGTTTACTTGCATTGAATTATCTCATGAAGGTCAGCTTGATTCGG
GCACATTAAAGACAGAGTCGGAAGAACACATTTCCCTAAGTTTTATTCTAATGTACAACACATGTGAT
CATTTGCGATGGGGTCTAGGCAGACAAGGCAGGTAACAGGGAGTCCTTCCAACCAGGGGTTGGAACAA
AGGAGGCTTGATTTGGTGACTCTTGAGACATTTGGCTCACTGCTGTGATGCTGTGAGAGATTAGCTGT
GCAATGTTTGGGCTCCTTAAAAGGAAGTTTATTTAAAATAAAACTTACCTGCACGTATGTAACACTGT
AGACACAGATCCTTCCCACAGTATATTTAATCTCTGCAGAATTCACTGGGAGGGGAGGGGAGCCAGTG
GGACCTCTTGGCTATTACACAGGTTGGCACTTCCAGAGAGAACAGTCTTGGCATCACAGGCTTCAGGC
ATACTCAAAGCTCTTCTCCCTTCTGATTCCAGTTTCTCCATGCCCTGCAGGGCCTCTTGGGATTATTG
TATTCTGGAAAGCAAACAAAGTTGGACACTGTCTCTTTAAATAATAGAGGCTGAGAACCTCTCAGGCC
ACCATGACATATCCCAGCATTGGACCAGCCCCTGAATAAACTGGAAAGACGCCTGGTCTGGCTT
ATGCTTTTGCTGCTTCTCTCCATAATAGTGTTGCACGTAGC
AGTCTTGGTCCTGCTCTTTGTTTCTACCATTGTATCACAGTGGATTGTGGGTAACGGCCACGCTACCG
ATCTGTGGCAAAATTGTAGCACGTCCAGCTCTGGTAATGTACACCATTGTTTCAGCAGTTCACCTAAC
GAGTGGCTCCAGTCAGTCCAAGCCACAATGATCCTGAGCATAATTTTTAGCATCCTCAGCCTTTTCCT
GTTCTTCTGCCAGCTCTTTACATTGACAAAGGGTGGACGGTTCTACATTACAGGGATATTCCAAATTC
TTGCGGGTCTGTGCGTGATGTCCGCCGCCGCCATCTACACCGTTAGGCACCCTGAATGGCATCTTAAC
TCCGACTATAGTTATGGTTTCGCCTATATCCTCGCATGGGTGGCTTTCCCTCTTGCCCTGCTTAGCGG
CGTAATCTATGTGATTCTCAGGAAGAGAGAAGATTATAAGGATGACGATGACAAATA
The MECP2 protein sequence is:
(SEQ ID NO: 44)
MAAAAAAAPSGGGGGGEEERLEEKSEDQDLQGLKDKPLKFKKVKKDKKE
EKEGKHEPVQPSAHHSAEPAEAGKAETSEGSGSAPAVPEASASPKQRRS
IIRDRGPMYDDPTLPEGWTRKLKQRKSGRSAGKYDVYLINPQGKAFRSK
VELIAYFEKVGDTSLDPNDFDFTVTGRGSPSRREQKPPKKPKSPKAPGT
GRGRGRPKGSGTTRPKAATSEGVQVKRVLEKSPGKLLVKMPFQTSPGGK
AEGGGATTSTQVMVIKRPGRKRKAEADPQAIPKKRGRKPGSVVAAAAAE
AKKKAVKESSIRSVQETVLPIKKRKTRETVSIEVKEVVKPLLVSTLGEK
SGKGLKTCKSPGRKSKESSPKGRSSSASSPPKKEHHHHHHHSESPKAPV
PLLPPLPPPPPEPESSEDPTSPPEPQDLSSSVCKEEKMPRGGSLESDGC
PKEPAKTQPAVATAATAAEKYKHRGEGERKDIVSSSMPRPNREEPVDSR
TPVTERVSDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MECP2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
MECP2-DNA (SEQ ID NO: 45)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTCCTTGTTTCTTCCCTTGCTCTATGCCCTA
CATCCAATCCTTTTGTTCAGTTCTGAAAACATATCTTGAATCTCACAACTTCTCAGAGCTGCACTGCT
GCCACCCTAGTTAAAGCTACCATCAACTCTTTCTCCTAGACTGTTCCAGGGCCTTGCAACTAGCCTTG
TGCTGTAGTTTTGTTTCATCACGTCCAGTTCTCCACTCTACACCTGCAACATAGATCAGACAGCTCCT
GGCTCAAAATCCTCTGAGGGCTTCTCATCTTAGAATAAACTCTCGGTTCTGGCCGGGTGCGGTGGCTT
ACGCCTGTAGTCCCAGCACTTTGGGAGTCCGAGGCGGGCGGATCACTTGAACTCAGGAGTTTGAGACC
AGCCTGGGCAACATGGTGAACTCCCATCTCTATCAAAAATACAAAAACTTAGCCAGGCGTGGTGGTTC
GCATCTGTGGTCCCAGCTACTTAGGACGCTGAGGAGGGAGGATCGCTTGAGCTCAGGGTGGACGTTGC
AGTGAGCCAAGATTGCGCCACTGCACTGCAGCCTGGGTGACAGAATGAGACCCCATCCCCACCCCCCC
CAAAAAAGAATGAACTCCCAGTTCTCATAGTGGCCCCAGCTGCCTTTCCAATCACATTCCCTACCACT
CTCCAGCAACACTGACTTCCTCGTTAGTCCCCAACATGCCAGGCATAGTCTCTCCTCATGTCCTTTGA
ACTTGCCTGGAATGTTCTTTCCCCAGATATTCATATGAGGGAGTAAAATGAGGGTGAAAACCAGCAGA
TATCTAAATAGCACCCCCTTCACTTAGTTTATCTTTCTCAAAGCCCTTATCACTATGTGAAATGATAT
ATTATACTTATTTGTATGCTAGTATGAATCTTCCCGGCAAGAATGTTAGTTTGCTGTCTGTTCAGTAC
CGTGCATCCAGAGCCTGGAAGAGTGCCTGGCACATAGCAGGTAGTCAATAAATGAATGGGGGCAAGCA
GCCAAATCAGAATCAGGTTTTCTTGCTAAGCATAGAACTAACAGAAGGATCATTGAATGGATTGGATA
ATGACTGGCATCAGGGTAAGGTCCCCTTAACAAACACTCCTGTCCTGAACACCTGGTTAGCTAACAGT
TTTCTCATACTCTTATTTTCCCAAAACACAATTGCTGGATCTCAGCTCCAAATCAACTCTTCTAGGAA
AGTGAAAAATTGCTGGATCTCAGCTCCCAAATCATATCTTCCAGGCAGAGCTAACATTGCCCCTTATT
CACACCTCCACCAAACCATCTGATCCAACAGTGACAGGTGTCACGAGGCCTTGGCATGCACTCTCTTC
CCCCGCCAGAGTTCTGCGAAAGCCAGGGTTGCGATTTGTTGTCAGTTTATTCCCCGCCTCTATGAGAG
TGTGAGCACTGGGCAGGCTCGGATGAAATAATGCATTGAGTAGGCCTCTGAAACCAAGGCCCCTCAGC
TGGGGCAACGTCAGGCTCCAGGGTGGGCAACTTTGCTGCTTCTGCCGAAGATAGTGATATTGAGAAAA
TGTGGGTGCAATGAAACGCTTATTGCAGCGCACTCGGTGCATCTGTGGACAGAGGGTCAATCGCCCCT
CAGAGCAGCGCAAACAGGCGTCCCAAGCCTAGGCCTTCACTTGCCCCAGCATCCGCAAGGGTCCATTA
ATCCTTAACATTCAAATTCCGCCCACTAAACCAGTCCCTCCGCGCCCAAGCCGCCTCTTTTCCCCAAA
CGACGGCCGAAAGCAGCCAATCAACAGCTGGAGGGGTCCGCCCCCTTTTCCCTGGCCGAAATGGACAG
GAAATCTCGCCAATTGACGGCATCGCCGCTGAGACTCCCCCCTCCCCCGTCCTCCCCGTCCCAGCCCG
GCCATCACAGCCAATGACGGGCGGGCTCGCAGCGGCGCCGAGGGCGGGGCGCGGGCGCGCAGGTGCAG
CAGCGCGCGGGCCGGCCAAGAGGGCGGGGCGCGACGTCGGCCGTGCGGGGTCCCGGCGTCGGCGG
ATGGCCGCCGCTGCTGCCGCGGCTCCCAGCGGCGGCGGT
GGAGGTGGTGAAGAAGAAAGACTTGAGGAGAAATCAGAGGACCAGGATCTCCAAGGTCTCAAGGATAA
GCCGTTGAAGTTCAAGAAGGTGAAGAAGGACAAGAAGGAAGAGAAAGAGGGCAAACACGAACCGGTCC
AACCTAGCGCTCATCATTCCGCCGAACCAGCAGAAGCGGGCAAAGCAGAAACGAGTGAAGGATCAGGT
AGCGCTCCTGCAGTTCCGGAAGCGAGCGCTTCACCGAAACAGCGCCGGTCTATCATCCGGGATCGGGG
ACCTATGTACGACGATCCAACGCTTCCGGAGGGATGGACGAGAAAGTTGAAGCAACGCAAGTCCGGAA
GAAGTGCTGGCAAGTACGATGTGTACCTGATTAACCCCCAAGGAAAGGCTTTCAGGTCTAAAGTAGAG
CTCATAGCTTATTTTGAAAAAGTGGGCGACACCTCTCTCGACCCTAACGATTTCGATTTCACCGTCAC
TGGCAGAGGCAGTCCTTCTAGACGCGAACAGAAACCCCCTAAAAAACCCAAGAGCCCCAAAGCCCCCG
GAACGGGACGAGGTCGCGGCCGCCCAAAGGGTAGCGGAACAACAAGACCAAAAGCGGCTACATCCGAA
GGTGTGCAAGTTAAGCGCGTGCTGGAAAAAAGCCCAGGAAAGCTCTTGGTCAAAATGCCATTCCAGAC
CTCACCTGGTGGCAAGGCAGAAGGTGGGGGCGCGACAACGTCCACCCAGGTAATGGTGATCAAAAGAC
CAGGCCGCAAGCGAAAGGCAGAGGCAGATCCGCAAGCGATCCCCAAAAAACGGGGCCGAAAGCCAGGA
AGTGTTGTCGCTGCTGCCGCGGCCGAAGCAAAGAAAAAAGCTGTCAAAGAGAGCTCCATTAGGTCAGT
ACAGGAAACCGTGCTGCCAATCAAAAAAAGAAAAACTCGGGAAACCGTCTCCATAGAAGTAAAGGAGG
TTGTCAAGCCCCTTCTTGTTTCCACCCTGGGAGAAAAATCAGGAAAAGGTCTCAAAACGTGTAAAAGC
CCGGGTCGAAAGTCAAAAGAATCATCACCAAAAGGCCGGAGTAGTTCAGCCAGTTCTCCGCCAAAGAA
AGAACACCACCACCATCACCACCACTCAGAATCCCCTAAGGCCCCAGTGCCTTTGCTCCCACCCCTTC
CTCCGCCGCCGCCAGAACCGGAGAGTTCTGAAGACCCCACTTCACCTCCGGAGCCACAGGACCTGTCC
TCTTCAGTTTGCAAAGAGGAGAAGATGCCTCGAGGCGGATCTCTGGAATCTGACGGGTGCCCGAAAGA
ACCCGCCAAGACGCAACCGGCGGTAGCAACCGCAGCAACCGCGGCCGAGAAATATAAGCATCGAGGAG
AAGGAGAACGCAAAGACATCGTTAGCTCTTCTATGCCACGGCCAAACCGGGAGGAACCAGTGGATTCA
CGAACGCCGGTCACAGAACGGGTCAGCGATTATAAGGACGATGACGACAAATA
The LAMP2 protein sequence is:
(SEQ ID NO: 46)
MVCFRLFPVPGSGLVLVCLVLGAVRSYALELNLTDSENATCLYAKWQMNF
TVRYETTNKTYKTVTISDHGTVTYNGSICGDDQNGPKIAVQFGPGFSWIA
NFTKAASTYSIDSVSFSYNTGDNTTFPDAEDKGILTVDELLAIRIPLNDL
FRCNSLSTLEKNDVVQHYWDVLVQAFVQNGTVSTNEFLCDKDKTSTVAPT
IHTTVPSPTTTPTPKEKPEAGTYSVNNGNDTCLLATMGLQLNITODKVAS
VININPNTTHSTGSCRSHTALLRLNSSTIKYLDFVFAVKNENRFYLKEVN
ISMYLVNGSVFSIANNNLSYWDAPLGSSYMCNKEQTVSVSGAFQINTFDL
RVQPFNVTQGKYSTAEECSADSDLNFLIPVAVGVALGFLIIVVFISYMIG
RRKSRTGYQSVDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for LAMP2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
LAMP2-DNA (SEQ ID NO: 47)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTTTGTTAAAGAAGTGATTAATAAGACTGC
CACAGACCTACTGTTTCAGAATCTCTGGGGAATGAGGTACAGGAATCTGTATGTTAAAAAAAAAAAAC
CCAAAACCAGATGGTTCTTTTGGAAACTAACACTTGAGAATCAGTGCTTTATTCCAACTCAAGATTTT
TAAATGCTTTCATCTGTTGAATATTTTAGGTTTTGTCTGTTCATCTATCAAGTATAGCAAACAGTATG
CTTAGTATGAACTCATTACAGAATATTTGTGTGTATGTACATAGGAAAAATATCTGGAAGTATAGATG
TGGGTGTGTGTATATATGTGTGTAAATATATATAATAATGTTAATAGTAGGAATACAGATGATCTCTA
TTTTTCCGCTTTATCCTTCTGTTTTATTTCTCTCATTTTTTTCTTCCTGTGTTTAAAAAAGATGCTTC
TTGTTTCTGAGCTCAATTCCCCCACCTGAGAACAGGGTGCTGTAACTAGGTGAATTTCAAGATCATGT
CTTGTTCCGATGGTCCGTGACTCCATACTACCCCCTAGGTTCCCTCGTCCATCTCACAGCATGAACTG
CATAGGTAACAACAGTGTTTGGAGAATAAGCATGTATTATTTTTGTATGTATTACGTTTGAGATGCCT
AGCAACCGTTTTTGTGCCCGCAAAATTTTTCTCTTCTTTGTCAAGGAGCCAAAACGGAAATAGTCTAC
TATCTACGGCCCTCAAAAGTTCCTCCTCTCTCCTTAGCCTTAGAAAATACCGTCCGCCATAGGCATGG
GCAAAGACCTCATGGCTAAAACACCAAAAGCAATCGCAACAAAAGTCAAAATTGACAAATGGGATCTA
ATTAAAAGAACTTCTGCACAGCAAAAGAAATTAGCATTAGCGTGAACAGGCAACCTGCAGAATGGGAG
AAAATTTTTGCAATCTACCCATCTGACAAAGGTCTAATATCCAGAATCTACAAGGACCTTAAACAAAT
TTACAAGAAAAAAACAACCCCATCAAAAAGTGGGCAAAGGATATGACCAGACACTTCTCAAAAAAAGA
CATTTATGCAGCAACAAACATGAAAAAAAGCTCATTATCACTGATCATTAGAGAAAGGCAAATCAAAA
CCACAATGAGATACCATCTCACGCCAGTCAGAATGGTGATTATTAAAAAATCAGGAAACAATAGATGC
TGGCGAGGCTGAGGAAAAATAGGAATGCTTTTACACTGTTGGTGGGAGTGTAAATTAGTTCAACTATT
GTGGCAGACAGTGTGGCGATTCCTCAAAAATCTAGAACCAGAAATACCATTTGACGCATGCACACGTA
TGTTTATTGCAGCACTATTTACAATAGCAAAGACTTGGAACCAACCCAAATGCCCATCAATGATAGAC
TAGATAAAGAAAACGTGGCACATATATGCCATGGAATACTATGCAGCCATAAAAAAATGAGATCATGT
CCTTTGCAGGGACATGGATGAAGCTGGAAGCCATCATCCTTAGCAAACTAACACAGGAACAGAAAACA
AAACACTGCATGTTCTCACTCATAAGTGGGAGTTGAACAATGAGAACACATGGACACAGGGAGGGGAA
CAACACACACGGGGGCCTGTCAAGGGGTGGGGGCCAAGGGGAGGGAGAGCATTAGGAGAAATACCTAA
TGCATGTGGGGCTTAAAACCTAGATGACGGGTTGATAGGTGCAGTAAACCACCATGGCACATGTATAC
CTATGTAACAAAGCTGCACATTCTGCACATGTATCCCAGAACTTAAAGTAAAATTAAAAAAAAAAAAA
AAAAAGAAAGAAAAAGAAAAAGAAAATGCCGTCCGCGCATATCTCTCAGGAGCATAGGAAGGGCTGTG
AACCAAAAAGCCAGGGCGTGGTCGCCCCGCCCACCGGCCGCTACATCACCACCCCTCTCGCCGCTTTC
AAGCGCGGAGATTGGCTGTAAGCAAGAAAGAGCCCCGCCCC
ATGGTCTGCTTTAGACTGTTTCCAGTACCAGGTTCTGGACTCGTGCTGGTGTGTCTTGTACTG
GGTGCAGTCCGATCTTACGCCTTGGAACTTAACCTCACTGATTCTGAGAATGCCACTTGTCTTTACGC
AAAGTGGCAGATGAACTTTACGGTGCGGTACGAGACCACGAATAAAACTTATAAGACCGTAACGATAA
GCGATCATGGGACCGTCACTTACAACGGCTCCATCTGCGGGGACGATCAAAATGGCCCAAAAATCGCT
GTCCAATTCGGCCCAGGGTTCAGTTGGATAGCCAACTTCACTAAAGCTGCATCAACCTATAGCATAGA
TTCTGTATCCTTCTCTTACAATACCGGAGATAACACAACGTTTCCCGATGCAGAAGACAAAGGCATAC
TCACCGTGGACGAGTTGCTTGCTATTAGGATACCGCTTAACGACTTGTTTCGCTGCAATAGTTTGAGC
ACCCTTGAAAAGAATGATGTGGTTCAGCATTATTGGGACGTACTCGTTCAAGCTTTTGTCCAGAATGG
TACGGTTTCAACCAATGAATTTCTCTGCGATAAGGACAAAACTTCCACAGTTGCCCCAACTATTCACA
CGACCGTTCCAAGCCCCACAACGACCCCGACTCCGAAAGAAAAACCAGAGGCCGGAACCTACTCAGTG
AATAATGGTAATGACACATGCCTCCTTGCTACGATGGGGCTCCAGTTGAACATCACACAAGACAAAGT
TGCGTCTGTCATAAATATTAACCCCAATACCACCCATAGTACCGGGTCCTGTCGATCTCATACTGCGC
TTCTCAGACTTAATAGCAGCACCATCAAGTACCTGGATTTCGTTTTCGCTGTAAAAAACGAGAATCGG
TTTTATCTCAAAGAAGTAAATATTAGTATGTACTTGGTAAATGGTAGTGTGTTCTCTATAGCGAACAA
TAACCTCTCATACTGGGATGCGCCTCTTGGTAGTTCCTACATGTGCAACAAGGAGCAAACAGTGAGTG
TCAGTGGGGCATTTCAAATCAATACGTTTGATCTTAGAGTCCAGCCATTCAATGTGACTCAGGGGAAG
TACTCTACGGCGGAAGAGTGTTCCGCGGACTCCGATCTTAATTTTTTGATCCCTGTCGCCGTGGGGGT
CGCCCTGGGATTTCTGATAATTGTCGTTTTTATAAGCTACATGATAGGCAGGAGGAAGAGTCGGACGG
GATACCAGTCTGTGGATTACAAAGATGATGATGACAAATA
The NAGLU protein sequence is:
(SEQ ID NO: 48)
MEAVAVAAAVGVLLLAGAGGAAGDEAREAAAVRALVARLLGPGPAADFS
VSVERALAAKPGLDTYSLGGGGAARVRVRGSTGVAAAAGLHRYLRDFCG
CHVAWSGSQLRLPRPLPAVPGELTEATPNRYRYYONVCTQSYSFVWWDW
ARWEREIDWMALNGINLALAWSGQEAIWQRVYLALGLTQAEINEFFTGP
AFLAWGRMGNLHTWDGPLPPSWHIKQLYLQHRVLDQMRSFGMTPVLPAF
AGHVPEAVTRVFPQVNVTKMGSWGHFNCSYSCSFLLAPEDPIFPIIGSL
FLRELIKEFGTDHIYGADTFNEMQPPSSEPSYLAAATTAVYEAMTAVDT
EAVWLLQGWLFQHQPQFWGPAQIRAVLGAVPRGRLLVLDLFAESQPVYT
RTASFQGQPFIWCMLHNFGGNHGLFGALEAVNGGPEAARLFPNSTMVGT
GMAPEGISQNEVVYSLMAELGWRKDPVPDLAAWVTSFAARRYGVSHPDA
GAAWRLLLRSVYNCSGEACRGHNRSPLVRRPSLQMNTSIWYNRSDVFEA
WRLLLTSAPSLATSPAFRYDLLDLTRQAVQELVSLYYEEARSAYLSKEL
ASLLRAGGVLAYELLPALDEVLASDSRFLLGSWLEQARAAAVSEAEADF
YEQNSRYQLTLWGPEGNILDYANKQLAGLVANYYTPRWRLFLEALVDSV
AQGIPFQQHQFDKNVFQLEQAFVLSKQRYPSQPRGDTVDLAKKIFLKYY
PRWVAGSWDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NAGLU and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
NAGLU -DNA (SEQ ID NO: 49)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGGACAACATGGTGAAATCCCATCCCTACAA
AGGTTAACTGGGCTTGGTGGCACGTGCCTGTAATCCCAGCTACTCAGGAGACTGAGACAGGAGAATGG
CTTGAACCTGGGTGGCTGAGGTTCCCGTGAGCTGAGATTAAAAAAAAAAATCATACTTCCCTAGTATC
TAAAGTTGATATCTGATTCCAGGCCTCTTTCAACTTTTTTTGTTTGTTTGTTTGTTTTTTTGATATGG
AGTCTCGCTCTGTCATCCAGGCTGGAATGCAAATGGCACGATCTTGGCTCACTGCAACTTCCACCTCC
AGCGTTCAAGCGATTCTCCTGCCTCAGCTTCCCAAGTAGCTGGGACTACAGGCGTGTGCCACCAAGCC
TGGCTAACTTTTTTTCTTTTTTTTTTTTTTGAGAGGGAGTCTTGCTCTGTCCCCCAGGCTGGAGTGCA
GTGGTGTGATCTTGGCTCACTGCAACCTCCGCCTCTCCGGTTCACGCCATTCTCCTGCCTTAGCCTCC
CGAGTAGCTGGGAGTACAGGCGCTCGCCAACACGCCCGGCTAATTTTTTGTATTTTTAGTAGAGATGG
AGTTTCACCGTGTTAGCCAGGAGGGTCTTGATCTCCTGACCTCGTATCCGCCCGTCTTGGCCTCCCAA
AGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCAGCACCTGGCTAACTTTTGTATTTTTAGTACAGA
CGGGGTTTCACTGTATGTTGGCCAGGCTGGTCTCAAACCCCTGACTTGAGGTGATCTGCAAGCCTCAG
CCTCCCAGAGTGCTGGGATTACAGGCGTAAGCCACCGCTCCTGGCCTAAGGTTGGCTATTTTTATGGT
TATTTCTTGATTATATGATAAACAAGGGGTGGGTTAGTAATGAATTTTTCAGAAAAGGGGTGGGGATC
CCCCCCAACTGAAGGTTCCTCCACTGTTTAGACCATATAGGGTAACTTCTGGACGTTGCCATGGCATT
TGTAAACTGCCTGGCGCTGCTAGGAGTGTCTTTAGCATACTAATGCATTATAATTAGCGTATAATGAG
CAGTGAGGACGATCAGAGGTCACCTTCCTGTCTTGGTTTTGGCAGGTTTTGACCAGTTTCTTTGCTGC
ATTCTGTTTTATCAGCGGGGTCTTGTGACCTTTTATCTTGTGCTGACCTCCTGTCTCATCCTGTGACG
AAGGCCTAACCTCCTGGGAATTCAGCCCAGCAGGTCTCTGCCTCATTTTACCCAGCCCCTGTTCAAGA
TGGAGTCGCTCTGGTTGGAAACTTCTGACAAAATGACAGCTCCTGTTATGTTGCTGCTGCTGCCGCCA
ATGGACAGCCTTTAACGTGCCCGCCAGCCCTGCTCCACCGCCGGCCTGGGCTCACATGGCCCCATCCC
TCCTCGAACCTCCTAGCCTGTTAGTTACTCAAATCTGCAAGCTCTCTGCCTTCTCAGGGCCTTCAATA
AATGCATTTCTTCTGTCTGGAAGGCTCTTCCTTTCCCTCTTCTAGCCAATTCCTATTCATCCCTGAGT
TTCAGATTAAAAGTCACTTCCTTTGGAAACCTTACTTCGCTACTTCGCTACTTACTGCACTACTTCGC
AGCATCACAACTATGATGGAAATCCTTACTTACGTTAAATATCTGGTTTCTAGGTCACCTCCCTGACG
GGGACGGTAGGGACCGTCTTCTCGTTCATCAGTAGGGAAGTAGCTATGGCAGTGCCTGATACAAAATA
AACTCCAAATGTGTATTTATTAGATGGTTGGATGGAAGTTATTTGCGTGTGAAAGCGCGTTTTACCCG
AAGGCGCTCTGTGAGGGCCAGCGGGTCCCCTTCGGCCCTGGAGCCGGGGTCACACGCTCCCCACCGCG
TGCGGTCACGAGACGCCCCCAAGGGAGTATCCTGGTACCCGGAAGCCGCGACTCCTGGCCCTGAGCCC
GGGCTTAGCCTTCGGGTCCACGTGGCCGGAGGCCGGCAGCTGATTGGACGCGGGCCGCCCCACC
ATGGAGGCGGTAGCCGTTGCCGCTGCCGTCGGAGTACTT
TTGCTCGCAGGAGCAGGTGGTGCAGCTGGTGACGAGGCTCGGGAGGCAGCGGCCGTACGCGCACTGGT
AGCTCGGCTGCTGGGGCCAGGTCCCGCAGCTGACTTTAGCGTGAGTGTGGAGCGGGCCCTCGCTGCGA
AGCCAGGCCTTGATACCTACTCTCTGGGCGGGGGAGGAGCGGCACGCGTGAGAGTTCGGGGAAGTACC
GGGGTGGCTGCGGCGGCGGGCTTGCATCGGTATCTTAGGGACTTTTGTGGGTGTCACGTCGCCTGGTC
AGGTAGCCAACTCAGGCTGCCACGACCTTTGCCAGCAGTACCCGGCGAGTTGACGGAAGCGACGCCAA
ATAGGTATAGGTACTATCAAAACGTCTGTACCCAGTCTTATTCTTTTGTATGGTGGGATTGGGCTCGC
TGGGAACGAGAAATAGACTGGATGGCACTTAACGGCATCAATCTTGCGTTGGCCTGGAGCGGGCAGGA
GGCAATCTGGCAGCGAGTGTATCTCGCATTGGGGCTCACACAGGCTGAAATAAATGAGTTTTTTACCG
GTCCCGCCTTCTTGGCTTGGGGCAGGATGGGTAATCTCCATACGTGGGATGGACCGCTCCCACCTTCA
TGGCATATAAAGCAGCTGTACCTGCAACATAGGGTGTTGGACCAAATGAGGAGCTTTGGAATGACACC
GGTACTTCCGGCATTCGCCGGTCACGTTCCTGAAGCGGTCACGCGAGTATTTCCGCAAGTGAATGTAA
CAAAGATGGGTTCATGGGGACACTTCAATTGTTCATATTCATGCTCTTTCCTGCTTGCGCCGGAAGAT
CCTATTTTTCCTATCATTGGAAGTCTGTTCCTTCGGGAATTGATCAAGGAGTTTGGAACAGATCACAT
ATATGGAGCAGACACTTTTAACGAAATGCAACCTCCGTCTAGCGAGCCCTCTTATCTGGCAGCTGCGA
CCACGGCGGTGTATGAAGCGATGACAGCTGTCGATACGGAAGCAGTCTGGCTCCTTCAAGGTTGGCTG
TTTCAACACCAACCGCAATTTTGGGGACCAGCCCAGATTAGGGCTGTGTTGGGTGCTGTGCCCCGGGG
TAGGCTCTTGGTGTTGGATCTTTTTGCGGAGAGTCAGCCTGTGTATACCCGAACGGCGAGCTTTCAAG
GTCAGCCGTTTATCTGGTGTATGCTTCATAACTTTGGCGGGAACCATGGTCTTTTCGGTGCCCTTGAA
GCCGTAAATGGGGGGCCAGAGGCTGCTCGATTGTTTCCTAACAGCACTATGGTAGGAACAGGTATGGC
ACCCGAGGGTATTAGTCAAAATGAGGTCGTATACAGTTTGATGGCAGAACTTGGGTGGCGCAAAGATC
CCGTACCTGATCTGGCAGCGTGGGTTACGAGCTTCGCGGCTCGAAGGTACGGAGTAAGTCACCCAGAC
GCTGGGGCCGCCTGGCGGTTGCTCCTGCGATCCGTCTACAACTGCTCAGGTGAGGCATGCCGCGGGCA
CAATAGAAGCCCACTCGTCCGACGACCATCCCTTCAAATGAACACTAGTATCTGGTACAACAGGTCTG
ACGTATTCGAGGCATGGCGCCTCCTCCTCACTAGCGCACCGAGTCTGGCTACCTCCCCCGCGTTTAGG
TACGACCTTCTGGACTTGACCAGACAAGCTGTGCAGGAGCTCGTGTCACTTTACTACGAAGAGGCCAG
ATCTGCATATCTGTCTAAGGAACTGGCATCCTTGCTTAGAGCGGGTGGGGTTCTGGCTTACGAACTCC
TTCCAGCACTGGACGAGGTGCTCGCGAGTGACAGTAGGTTTCTCCTCGGGTCATGGCTGGAACAAGCA
AGGGCCGCGGCCGTTTCTGAAGCCGAGGCTGACTTTTACGAACAGAACTCTCGATACCAGTTGACGCT
GTGGGGACCCGAGGGGAATATCTTGGATTACGCGAACAAGCAGCTGGCAGGTCTGGTAGCCAACTACT
ATACGCCGAGGTGGAGGCTCTTCCTCGAGGCTCTTGTCGATTCCGTCGCCCAAGGGATACCCTTTCAG
CAGCACCAATTCGACAAGAACGTTTTTCAACTGGAACAGGCTTTCGTACTTTCCAAACAACGCTATCC
CAGCCAGCCTCGGGGTGACACAGTTGACCTGGCAAAAAAAATCTTCCTTAAATACTATCCAAGATGGG
TCGCCGGTAGTTGGGATTATAAAGATGATGATGACAAGTA
The ARSB protein sequence is:
(SEQ ID NO: 50)
MGPRGAASLPRGPGPRRLLLPVVLPLLLLLLLAPPGSGAGASRPPHLVFLL
ADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYYTQPLCTPSRSQLLTGR
YQIRTGLQHQIIWPCQPSCVPLDEKLLPQLLKEAGYTTHMVGKWHLGMYRK
ECLPTRRGFDTYFGYLLGSEDYYSHERCTLIDALNVTRCALDFRDGEEVAT
GYKNMYSTNIFTKRAIALITNHPPEKPLFLYLALQSVHEPLQVPEEYLKPY
DFIQDKNRHHYAGMVSLMDEAVGNVTAALKSSGLWNNTVFIFSTDNGGQTL
AGGNNWPLRGRKWSLWEGGVRGVGFVASPLLKQKGVKNRELIHISDWLPTL
VKLARGHTNGTKPLDGFDVWKTISEGSPSPRIELLHNIDPNFVDSSPCPRN
SMAPAKDDSSLPEYSAFNTSVHAAIRHGNWKLLTGYPGCGYWFPPPSQYNV
SEIPSSDPPTKTLWLFDIDRDPEERHDLSREYPHIVTKLLSRLQFYHKHSV
PVYFPAQDPRCDPKATGVWGPWMDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for ARSB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
ARSB-DNA (SEQ ID NO: 51)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGAAATATTTATTAATTACAAGAAGAAAATAT
TAACCTTACAATGAGGAAATGTTTACCTTAACAAAGTTATCCCATAAGAAAGCAATTCAGCATCATGT
GCCTCTTAATAGGAAGCACCGAGAAACATACCACATCACTTTTTGTGGTATTCCTGCACAAATCCATA
ACCTCTATCTAATTGTGAAGAAACATCAAACTCCAATTGAGAGATTTTATAAAATAACTAGCTTGTAC
TGCACATTATGTGTTCAATACATAGATGGAAAATAGAATTAACTCTTCAATTTGCACATTTCCAGAGC
ACTATTAACATATGCTTTTATTTTAAAAACATAGGACGTAAGAATCTGTGCAAGTTTAGCTAGTTTCA
GGGGAAGTTGGTTAAAGGAGGAATTGTTCCTGCAGATTAGCACCCATCAATTATTTCTTCTTAATTTT
TATCAAGGAGAATAGGAAGGATTACGGGGGAGAAAGACACAAAACCACAGCGGAAATTCTCAGTCCTT
CAAGGTCTTCTACAGGGTGTTTAAATGAAAAGTTCAACCCTTGACATAATGAGTCAAACAGTTCTCTC
AAAAGTTATTCTTTGAATTTAATGCTAAAATTTTCACTTTTTTCTGCTAAATTTCATTGATTCCACTA
GAGATTAAAGTGCATACAACATAAACTAATCTACTTCATGCAAAGAAAAAAAGTGTATGTAAGAGGCA
AACATTTCATGTGTTAAAGGATTCTTGGGGAAAAAAAGGTAAAATCATGACCCTCATACAAATATAAA
AGTGAATACATGATTTTATTTAACTCATTAATAAGGAAATTGGTAAGGTGTTAAAACCAATTCAAAGG
ACAATCCAAAGAACAGATCAGGAATACTAAAATAAATATGCAAGCGGAGGTGAAACTGTTTTCCTTGG
TAGTGGTGGAGGGGAAGGATTGCTACTCCGCTGGATAAAGTTCATTTGTGTATATATAAATAAGAATT
ATTTTCCATTGTTATTTATCTATAACTTATAAAGTTGTAAACAACTTCCACGGAATCAGACTCAACCT
GGAAGGGTATGGTCTCTAGGCAATGCAAAAATTTTCCCCTACACCTGTTAACAACTATAATATCTCCA
GACAGAGTAGACAGAAAGTCTGGATGGCAACGGGAATCTACTGGTCATACGGCTAACTTCCTAATTCA
ATAAGCACGTGACTAAAGGATTTTTTCCTTCCACTCAGATATTTCAGGCTAACTAGATACTGTGTGCT
TCTTAGTGTCACTGCTTAGTGGGGGAGCCAGCTCTGAGTGGGGTCATATCCGGACAAGCGAATGAGCT
ATTTATTCAATGACCACGCAACACTCCAAATCCTCCCAGGGCAACTTGAAAGTAACCGCACCTTCCAA
AGGGCACCGTGCAATCAGACTGTGTGTTTGGCCTCCTGTTTGCTAGTGGGGAGGAAGCGGCTTCATGG
GTGTACACTACGCATAAATGAATGTGAAAGGCTATTTAGACCTCTGCCTTTTCACCGTCCTCCCACCT
GCCACAGGCTGGGCTCTTGTGCTAGAAATGACTTGCTAGCTAGACATCATGGTTCAGGATCTGAGTCA
GAGGTTTAACCATTTATAAGCTTTTTTCTTATGAAAAATTGGCACTAATTATAATGTCTAACTGTCAG
AGTTGTTGCAGGCTTTACAGGAGACGCGGGCTGTGAAGATGCTTTGTAAATTGTGAAGCGTTATTAAA
GAACACATCTTTTTTTTTTAGGAAACCACAGTGCAAATTTAATTGCCGGGGAAGATAACGGGCCTTGG
TGCCCTCCAAGCGTCAGCTGAGTTTCCAAGAAGCCGGGCAGCGGGCGCCCGCGGGTTCGTCTCTGGCT
CCTCCTCCGCCACAGCAGCCGGGGGCCCGGGTCGGAGGCGGCGGGGGCCGAGCGCCCGGCCTCGCAAG
CCCACGGCCCGCTGGGGGTGCCGTCCCGCGCCGGGGCGGAGCAGGCCCCGGCAGCCCAGTTCCT
ATGGGCCCCCGGGGCGCAGCGAGCCTCCCCAGAGGGCCAGG
ACCAAGGAGGCTCCTTTTGCCAGTCGTCTTGCCGCTTTTGCTCCTTTTGCTTCTCGCGCCACCCGGCA
GTGGGGCAGGAGCTTCTCGCCCACCTCACCTTGTCTTCCTGCTTGCTGACGACCTTGGATGGAATGAT
GTGGGTTTTCACGGTTCCCGGATTCGAACACCACACTTGGATGCTCTGGCTGCGGGGGGCGTACTGCT
CGATAATTATTACACACAACCGTTGTGCACACCGTCTCGGAGTCAGCTTCTGACGGGACGATATCAAA
TAAGGACTGGGCTGCAACATCAGATTATATGGCCATGTCAACCCAGTTGCGTGCCCCTTGACGAGAAA
CTCCTGCCTCAGCTGTTGAAGGAGGCTGGATACACGACACATATGGTCGGCAAGTGGCATCTGGGAAT
GTACAGGAAAGAGTGTCTCCCAACCCGGCGCGGATTCGATACGTATTTTGGGTACTTGTTGGGCTCAG
AAGATTACTATTCACACGAAAGGTGCACTCTTATCGACGCACTCAACGTTACGCGCTGCGCACTTGAT
TTCCGAGATGGAGAGGAAGTTGCAACTGGGTATAAGAATATGTATTCAACAAACATCTTTACTAAGCG
GGCAATAGCCCTCATTACTAATCATCCCCCCGAAAAACCGCTGTTTCTCTATCTCGCCCTGCAGTCAG
TCCATGAGCCGCTGCAGGTGCCTGAGGAGTACCTCAAACCATACGACTTCATACAAGATAAGAACCGA
CACCATTATGCGGGTATGGTCTCTCTGATGGACGAGGCTGTCGGGAATGTTACTGCAGCATTGAAATC
TTCCGGCCTTTGGAACAACACAGTCTTCATATTTTCTACGGACAATGGCGGGCAGACTCTTGCCGGTG
GCAATAACTGGCCTCTTAGGGGTCGCAAGTGGTCCCTCTGGGAAGGAGGCGTCCGCGGTGTAGGGTTT
GTAGCGAGCCCCCTCCTTAAACAAAAAGGAGTTAAAAACAGGGAACTTATTCACATTTCCGATTGGTT
GCCCACGCTCGTCAAGCTCGCGAGGGGTCATACAAACGGGACAAAACCGCTTGACGGGTTTGATGTAT
GGAAAACCATTTCTGAGGGGTCTCCTAGCCCCAGGATCGAGCTGTTGCATAACATAGACCCAAACTTT
GTAGACTCCTCACCCTGTCCCCGAAATTCAATGGCCCCTGCCAAAGATGATTCATCCCTCCCTGAGTA
CTCCGCTTTTAACACAAGCGTACATGCCGCTATTAGGCACGGCAATTGGAAGCTGCTGACCGGGTATC
CTGGTTGTGGTTATTGGTTCCCTCCCCCCTCACAATACAACGTGTCTGAAATACCGAGTAGTGATCCG
CCGACAAAAACCCTGTGGCTGTTCGATATTGATCGAGACCCTGAAGAACGCCACGATCTCTCCCGGGA
ATACCCCCACATTGTCACCAAGCTTCTTTCACGATTGCAATTTTACCACAAGCATTCAGTACCCGTTT
ACTTCCCCGCCCAGGACCCAAGGTGCGATCCTAAAGCAACGGGGGTTTGGGGACCATGGATGGACTAC
AAAGATGATGACGATAAATAG
The GUSB protein sequence is:
(SEQ ID NO: 52)
MARGSAVAWAALGPLLWGCALGLQGGMLYPQESPSRECKELDGLWSFRAD
FSDNRRRGFEEQWYRRPLWESGPTVDMPVPSSFNDISQDWRLRHFVGWVW
YEREVILPERWTQDLRTRVVLRIGSAHSYAIVWVNGVDTLEHEGGYLPFE
ADISNLVQVGPLPSRLRITIAINNTLTPTTLPPGTIQYLTDTSKYPKGYF
VQNTYFDFFNYAGLQRSVLLYTTPTTYIDDITVTTSVEQDSGLVNYQISV
KGSNLFKLEVRLLDAENKVVANGTGTQGQLKVPGVSLWWPYLMHERPAYL
YSLEVQLTAQTSLGPVSDFYTLPVGIRTVAVTKSQFLINGKPFYFHGVNK
HEDADIRGKGFDWPLLVKDFNLLRWLGANAFRTSHYPYAEEVMQMCDRYG
IVVIDECPGVGLALPQFFNNVSLHHHMQVMEEVVRRDKNHPAVVMWSVAN
EPASHLESAGYYLKMVIAHTKSLDPSRPVTFVSNSNYAADKGAPYVDVIC
LNSYYSWYHDYGHLELIQLQLATQFENWYKKYQKPIIQSEYGAETIAGFH
QDPPLMFTEEYQKSLLEQYHLGLDQKRRKYVVGELIWNFADFMTEQSPTR
VLGNKKGIFTRQRQPKSAAFLLRERYWKIANETRYPHSVAKSOCLENSLF
TDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GUSB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
GUSB-DNA (SEQ ID NO: 53)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTGCCCAGCTAAATATGGAGATGCGGTTTCT
CCATATTGGTCAGGCTGGTCTCGAACTCCCAACCTCAGGTGATCTGCCTGCTTCAGCCTCCCAAAGTG
CTGGGATGACAGGCGTGAGCCACCGCACCTGGCCAAGGCACTTGGTTTCTTAGATCACCCACTTGGCC
CTCTTCCAAGTTGTACTTTCCTTCTTTCCTTCCTGTTCTAAAGTTTTTTAATATTTTTTTTTTTCCTG
AAATGGCATCTCACTCTGTAGCCCAGGCTGGAGTGCGGTGGCGTGATCTCAGCTCACTGCAACCTCTG
CCTCCTGGGTTAAAGCATTTCTCCTGCCTCAGCCTCCCAAATAGTAGGGATTACAGGTGCCTGCCACC
ACGCCTGGCTAATTTTTGTATTTTTAGTAGAGATGGGGTTTCTCCACGTTGGCCAGGTTGGTCTCAAA
CTCCTGATATCAAGTGATCCTCCCGCCTTGGCCTCCCAAAGTGCTGGAGTTTGGAGTTACAGGCCTGA
ACCTCTGTGCCTGGCCTGCTTTTTTTTTTAGACTGAGTCTTGCTCTCTCGCCAGGCTGTAGTGCTGTG
GTGCGATCTCGGCTGACTGCAACCTCTGCCTCCCGCGTTCAATCGATTCTCCTGCCTCAGCCTCCCGA
GTAGCTGGGACTACGGGCGCATGCCACCATGCCCAGCTAATTTTTTAGTAGAGATGGGGTTTCATCAT
ATTGGCCAGGCTGGTCTCAAACCCCTGACCTCGTGATCCCCCCACCTCCGCCTCCCAAAGTGCTGGGA
TTACAGGTGTGAGCCACTACGCTCAGCACTGGCCTGCTTTTTAACAAGCTTTTACTACTGCTCTGCAG
CTTACCTCCCTCTGGCTTTCTGCCTTATGCCCCTCAGTGCAATTCTTTCTTCTGAGGAGGCAAGAATT
GAGGTTGTTGCTGATGTGTAGGGATTCACCACCCGGAACTCCACCAGTAACAGGTCGAGGATGCTAGT
TGAAAATGTTATGTAAGCTGCATGCTTTTTACAAATGGTAGTGGTTCTCATGTCCAGCAATGGCCACT
GCACCGTCCCTGTATGAAAGTCCCCTCCATAAATCTATGTCTCCTTTGCTGTCTCCAGATCTCCTCCT
CTACCTCTCCCACACGGTGCCTTCCCTACTGGAGTAAACTGGGGTCCCGCAGGGCACCCTTTCCCTGC
AATTTTTTTTTTTTTTTTGAGACAGAGTCTCGCTCTGTTGCCCAGGCTGGAGTGCAGTGGTGCGATCT
CGGCTTACTGCAGCCTTTGCCTCCCGGGTTCAAGCGATTCTCCTACCTCAGCTTCCTGAGTAGCTGGG
ATTACAGGCACGCACCATCACGCCCCGCTAATTCTTTTTTTTTTTTTTGTATGTTTACAAAATAGGGA
CGGGGTTTCACTATCGTTGGCCAGGCTGGTCTCGAACTCCTGGCCTCAAGTGATCTGCCCCCCTCGGG
TTCCCAAAGTGCACCTGGCCTCTCTCCCTGCATCTTTATGTGCCTGCAACACCAAGAGGGAGCTCTTG
GCCCCTGGGTTAAGGTCAGGGCTCCAGAAGCCCAGGGTCAAGGCTATGGCCGCATCCCAAGGACGTGC
ATCCCTGCAAGAGGCTGCATCAGACAGGCATGGAAGAGGCGCCGCTGGGGCCTCCTTGAATTCCTGCT
GGGAAAAGCAAGTGGAGGTGCTCCTTGAAGAAACAGGGGGATCCCACCGATCTCAGGGGTTCTGTTCT
GGCCTGCGGCCCTGGATCGTCCAGCCTGGGTCGGGGTGGGGAGCAGACCTCGCCCTTATCGGCTGGGG
CTGAGGGTGAGGGTCCCGTTTCCCCAAAGGCCTAGCCTGGGGTTCCAGCCACAAGCCCTACCGGGCAG
CGCCCGGCCCCGCCCCTCCAGGCCTGGCACTCGTCCTCAACCAAGATGGCGCGGATGGCTTCAGGCGC
ATCACGACACCGGCGCGTCACGCGACCCGCCCTACGGGCACCTCCCGCGCTTTTCTTAGCGCCG
ATGGCGAGAGGCAGTGCAGTAGCCTGGGCTGCTTTGGGACC
ATTGTTGTGGGGGTGCGCTCTCGGACTTCAGGGCGGTATGCTCTACCCTCAAGAGAGTCCCTCCAGGG
AATGTAAGGAGTTGGACGGCCTCTGGTCCTTCAGAGCCGATTTCAGTGACAATCGCCGCAGAGGGTTC
GAGGAGCAGTGGTACCGCCGACCGCTCTGGGAGTCAGGCCCAACCGTAGACATGCCAGTCCCATCTTC
ATTCAATGACATAAGCCAGGACTGGAGGCTGCGACACTTCGTCGGGTGGGTATGGTATGAGCGCGAAG
TGATCCTCCCTGAACGGTGGACTCAGGACTTGCGGACGAGGGTAGTACTTCGGATAGGTAGTGCTCAC
TCCTATGCTATTGTCTGGGTGAACGGAGTGGATACTCTGGAGCATGAGGGTGGCTATCTTCCTTTTGA
AGCTGACATCAGTAACCTGGTGCAAGTGGGGCCGCTGCCTTCCAGACTGCGAATCACCATCGCTATCA
ATAATACTCTGACCCCCACTACGTTGCCGCCAGGCACCATCCAGTATTTGACCGACACCTCTAAATAC
CCCAAGGGCTATTTTGTGCAAAACACTTACTTTGATTTCTTCAACTATGCCGGCCTGCAAAGATCTGT
GCTGCTTTACACCACTCCGACGACCTATATAGATGACATAACCGTGACGACGAGTGTCGAACAAGACT
CAGGTCTCGTCAACTACCAGATTAGTGTAAAAGGCAGTAATCTTTTTAAGCTCGAAGTGAGGCTTTTG
GATGCTGAAAATAAGGTGGTGGCAAATGGAACGGGCACACAAGGCCAACTTAAAGTGCCGGGGGTAAG
TCTGTGGTGGCCGTATCTTATGCATGAACGACCCGCTTATCTCTACAGTCTCGAAGTCCAATTGACGG
CACAAACAAGTCTTGGTCCTGTGAGTGATTTCTATACGTTGCCTGTGGGCATAAGGACTGTAGCTGTG
ACAAAGTCCCAATTTCTTATAAACGGTAAGCCCTTCTACTTTCATGGCGTCAACAAACATGAGGACGC
TGATATTCGCGGAAAAGGGTTTGATTGGCCTCTCCTGGTCAAGGACTTCAACCTTCTCAGATGGTTGG
GCGCGAACGCCTTTAGAACAAGCCACTATCCGTATGCAGAGGAGGTCATGCAAATGTGCGACAGATAT
GGGATTGTTGTAATCGATGAATGTCCCGGCGTGGGCTTGGCGCTCCCCCAATTTTTTAATAACGTGTC
TCTTCACCACCATATGCAAGTAATGGAGGAGGTAGTACGCCGCGACAAGAACCACCCCGCGGTAGTTA
TGTGGTCAGTAGCGAATGAACCAGCTTCTCATCTGGAAAGTGCCGGTTACTACCTCAAGATGGTGATA
GCCCATACAAAGTCTCTCGACCCTTCCCGCCCCGTGACATTCGTATCAAACAGCAATTATGCAGCCGA
TAAAGGCGCCCCATACGTAGACGTTATATGTCTTAATAGCTATTACTCCTGGTATCACGACTACGGTC
ATTTGGAACTCATTCAGCTGCAGCTCGCCACGCAATTCGAGAACTGGTACAAGAAATATCAGAAGCCA
ATTATACAGAGTGAATATGGTGCTGAAACAATCGCTGGATTCCATCAAGACCCACCATTGATGTTTAC
CGAGGAGTACCAGAAAAGTCTCCTCGAGCAATATCATCTTGGACTGGACCAAAAGCGACGAAAATACG
TAGTAGGGGAACTTATTTGGAATTTTGCCGATTTTATGACGGAACAGAGCCCTACACGAGTTTTGGGG
AACAAAAAGGGCATTTTCACCCGGCAACGGCAACCCAAGAGTGCCGCCTTCCTTCTTAGAGAAAGATA
CTGGAAGATTGCTAACGAAACACGCTATCCCCACTCTGTTGCTAAGAGCCAATGCTTGGAAAACTCCT
TGTTTACAGACTACAAGGATGATGACGATAAATA
The SLC19A3 protein sequence is:
(SEQ ID NO: 54)
MDCYRTSLSSSWIYPTVILCLFGEFSMMRPSEPF
LIPYLSGPDKNLTSAEITNEIFPVWTYSYLVLLL
PVFVLTDYVRYKPVIILQGISFIITWLLLLFGQG
VKTMQVVEFFYGMVTAAEVAYYAYIYSVVSPEHY
QRVSGYCRSVTLAAYTAGSVLAQLLVSLANMSYF
YLNVISLASVSVAFLFSLFLPMPKKSMFFHAKPS
REIKKSSSVNPVLEETHEGEAPGCEEQKPTSEIL
STSGKLNKGQLNSLKPSNVTVDVFVQWFQDLKEC
YSSKRLFYWSLWWAFATAGFNQVLNYVQILWDYK
APSQDSSIYNGAVEAIATFGGAVAAFAVGYVKVN
WDLLGELALVVFSVVNAGSLFLMHYTANIWACYA
GYLIFKSSYMLLITIAVFQIAVNLNVERYALVFG
INTFIALVIQTIMTVIVVDQRGLNLPVSIQFLVY
GSYFAVIAGIFLMRSMYITYSTKSQKDVQSPAPS
ENPDVSHPEEESNIIMSTKLDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SLC19A3 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
SLC19A-DNA (SEQ ID NO: 55)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGCTATGCATGAATGAATGAATTCCTCAATAT
CTCTCTCTGATTTAGACTGTGGCTATGAGATATTAGAGAATCAGAGTAAACTTCTCAAGGTCCAATTT
GAACTCATTTTCTTCAAGAGGTGTGAAGGAAATCATGACACCTTCAGCCTTTAAGAAAATTTCACAAT
ATTCTTTGGGAGGACCCAGCAATTTGCAAGGTTGCACAATGAGCAGGGCACTCCTACACCTAAGGTTC
AGCTCAGGACTTTTCACAAATCATAGGAAGATGAAAATAGAAAACGCAGAGTCGTAGGACAGAGAACC
AAGACACCTCGGGGTGTTTTAATCCATTTCACTTCCACTGGTAGCCCTTAGAAGCCACGCAGTGTTTA
TCTTTAGGGAGGGTTTTTCAAGTCCACCAAGAGATGAACAGAAATAAAAATATTTTTTCCATTTTAAC
CAATAAGAACCTTGTAATGCTTTAAAAAAATTCTCTGTTTAATAAGAAGTTTCACTTTAATATATAAA
CTCTTTGCAGGCTAAGCGTAGTGGCTCATGCCTGTAATCCCAACACTTTGGGCGGGCAAGGCAGGAGG
ATCCTTTGAGCCCAGGAGTTCAAGACCAGCCTGGGCAAGATAGTGAGACTCTGTCTCTACCAAAAAAA
AAAAACAAAAAAATTAATGTGACGTGGTGGCACCCACCTGCAAGCCCAGCTACTTGGGAGGCTGAGGC
AGGAGGATCAGTGTGCCTGGGAGATTGAGGTTGCAGTGAGCTGGGGTTGCACCACTGCACTCCAGCCT
GGGAGATAAAGTGAGACTTTGTCAAAAAAAAAAAAAAAAGAAAGAAAGAAAGAGAAAAGAAAAGAAAA
GAGGCCAGGTGGCCGGGTGCTGTGGCTCACACCTGTAATCCTAGCACTTTGGGAGGCCGAGGCGGGTG
GATCACCTGAGGTCAGGAGTTTGAGACCAGCCTGGACAACATGGTGAAACCCCATCTCTACTAAAAAT
ACAAAAATTAGCTGGGTGTGGTGACGGGCGCCTGTAATCCCAGCTACTAGGGAGGCTGAGGCAGAAGA
ATTGCTGGAACCCGGGAGGTGGAGGTTGCAGTGAGCCAAGATCGTGCCATTGCACTCCAGCCCGGGGC
CAACAACAGCGAGGCTCCATCTCAAAAAAAAAAAGAAAGAAAGAAAGAAAGAAAAAAGACCAGGCGCG
GTGGCTCACGCCTGTAATCTCAGCACTTTGAGAGGCCGAGGCAGGCGGATCACGAGGCCAGGAGTTCG
AGATGAGCCTGGCCAATATGGTGAAACCAAACCCCGTCTCTACTAAAAACACAAAAATTAACTGGGCG
TTAATTTTTGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCGGAGGGTTGTAGTGAGCCGAG
ATCGCGCCACTGCACTCCATCCTGGGCGACAGAGGGAGACTCTGTCTCAAAAAAAAAAAAAAGAAAGA
AAGAAAAGAGAAAAGAAAAGAAAAAGAAGAAGAAAAGAAAAAATTGTTTGTATCAGATTTTCAAAGTG
CCAGGAAACCATCCCACTCTACCTCCTTTAAAAAAAAAAAGTGCAGAGTGATTATAACCACTGGCTCT
GGAGCCAGGAGCCCCAACTAAAACCCAGGCTTCTCTATTTACTAGGCCTACTTCCTTCCGCCTCACTT
TCTTCATGTGTAGAGTGGGGGTGACAGCCAGCCAGCCCTCTCTCCTAAGCTTTTGGAGAGAAATAAAT
GGATTCATAAGAAAGGACATATTTGTAAATAAAGCAAACGATCGCTGTTGGATTCAGGCCCTCTTGCT
TCATTATGCTGAATGTCAGTGTATTACTTAAGTTGTTCCTTTCAGCAGAGTTGACTGTTTCTGCCCAG
AAAACCGGCCCTGGGCCAGGAAAATCTGGGCTTCCACACTGGGATGAAAGGTCTGGACGCCCGGATTC
GCATATGCAAAGCGTGGGGGCGTGGCCCCGGGCTCCGGGCCAGGCAGGCTCCGCCCCCTTCCCACC
ATGGACTGTTACCGGACCTCACTCTCTAGCAGTTGGATC
TACCCCACAGTCATCTTGTGCCTCTTTGGATTTTTCTCCATGATGCGGCCAAGCGAGCCGTTCCTTAT
ACCATACCTTAGCGGACCCGACAAAAACCTTACGAGCGCGGAAATTACGAACGAGATCTTCCCGGTAT
GGACCTACAGTTATCTTGTGCTTTTGTTGCCTGTCTTTGTCCTGACTGATTACGTTCGGTACAAGCCA
GTTATAATACTGCAGGGGATTTCCTTCATCATTACCTGGTTGTTGCTGCTCTTTGGACAGGGCGTAAA
AACTATGCAAGTAGTAGAGTTTTTCTACGGCATGGTTACCGCCGCAGAAGTGGCCTACTATGCCTACA
TCTACAGTGTGGTAAGCCCAGAGCATTACCAAAGAGTGAGTGGATATTGTAGATCAGTTACCCTTGCC
GCCTACACCGCGGGTTCCGTCTTGGCGCAGCTCCTGGTCTCACTTGCCAATATGTCCTACTTCTATCT
TAACGTTATTAGCCTCGCCTCCGTTAGCGTCGCCTTTTTGTTTTCCTTGTTTCTGCCAATGCCGAAAA
AAAGTATGTTTTTTCACGCAAAACCAAGTAGGGAGATCAAGAAGAGCAGCTCTGTTAATCCCGTTCTG
GAAGAGACACACGAGGGAGAGGCTCCAGGCTGCGAAGAACAGAAACCTACCAGCGAGATACTGTCTAC
ATCAGGAAAGTTGAACAAGGGACAGTTGAACTCACTCAAGCCAAGTAACGTCACAGTTGATGTGTTTG
TGCAATGGTTCCAGGATCTCAAAGAATGTTACAGTTCAAAAAGACTTTTTTACTGGAGCTTGTGGTGG
GCATTCGCAACCGCCGGTTTCAATCAAGTGCTTAACTATGTTCAAATCCTTTGGGATTACAAAGCCCC
AAGTCAGGACTCATCCATCTATAACGGCGCAGTCGAGGCGATTGCTACATTCGGAGGCGCTGTTGCAG
CGTTCGCCGTGGGCTACGTCAAGGTCAACTGGGATTTGCTGGGTGAGCTGGCTCTCGTGGTATTCTCC
GTCGTGAACGCAGGATCTCTTTTCTTGATGCACTACACTGCAAACATCTGGGCGTGCTACGCCGGGTA
CCTTATCTTTAAATCCAGTTACATGCTTCTCATCACTATCGCGGTTTTCCAGATTGCGGTAAATCTCA
ATGTCGAACGATACGCGCTCGTATTCGGCATAAATACTTTCATAGCGTTGGTTATTCAGACAATAATG
ACGGTGATCGTTGTAGATCAAAGAGGGCTGAACCTCCCCGTGTCCATTCAGTTCCTGGTGTATGGTAG
CTACTTCGCTGTTATAGCTGGAATATTCCTTATGCGCTCAATGTACATTACATACAGCACCAAATCCC
AGAAAGATGTGCAGTCTCCGGCTCCGTCTGAAAACCCCGACGTCAGTCATCCGGAGGAGGAGTCTAAC
ATCATAATGTCAACGAAACTTGATTATAAGGATGACGATGATAAATA
The PLP1 protein sequence is:
(SEQ ID NO: 56)
MGLLECCARCLVGAPFASLVATGLCFFGVALFCG
CGHEALTGTEKLIETYFSKNYQDYEYLINVIHAE
QYVIYGTASFFFLYGALLLAEGFYTTGAVRQIFG
DYKTTICGKGLSATVTGGQKGRGSRGQHQAHSLE
RVCHCLGKWLGHPDKFVGITYALTVVWLLVFACS
AVPVYIYFNTWTTCQSIAFPSKTSASIGSLCADA
RMYGVLPWNAFPGKVCGSNLLSICKTAEFQMTFH
LFIAAFVGAAATLVSLLTFMIAATYNFAVLKLMG
RGTKFDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PLP1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
PLP1-DNA (SEQ ID NO: 57)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGGAGTTGGGAACCTTAAGGCACTGGGATGA
GTGAGACACGGTCACCTGGCTGGGTCCCTTTTCTGGCCCTGGGCATAAGAACAAGCATAAGAACAAGG
CGAAGACAGGGAATGTGGAGAGAGAAAAAGGAAACAGAGACAGACACATAGAGAGAAACAGAGACAGA
GACAGGTAACAGAGACAAAGAGATTGAGACTTGGGGAGAGGATAGAATGAATATTAAGGCAATGGAGA
TGGAAGAAAGGAGAAGAGAAATGTGTGTTAAGGGAATGTGGTTGATAAATTGGTATCTGTGGGTTTAT
TGGGAACACATATTTTCTTTCCAGTAGAGTTGCTGTCCCCAGAGCTGCTGCTGAGAACTCAGGGGAAG
CTTTGTGAGAGGGCTCAGTCTGAGTGATGTCCCCTGTGTGGAGAGCTGTCTCATCTATTCGAGCTGTG
AAGGATCATTTGCCTCATCCTCTAAATCTGAACTCCCAAAGTTTGGGCTCACTCCTGCCATCTGATGA
GCTGAGGAGACACATTTGGCGATTTCTTGCTCTTGGTCCTCCCCCTTCTCCAGGGCCATTCCGACAGT
GACCATCCAGAAGTTTATTGCTGGCTCAATCCTACAGTTGAGCTTCCAAAGCAGGCATAGTCTGTGGC
TGGCGAGCAGGGCTGGGGAGGGCGAGGGGCTCTAGGACCCTTTTCCATCAGTCACATGGCCTTAGTCT
CGTCTGCTCTGGAAAGCTACTATTATACCGTTTTGCAAGGGGCAGCATTTCCAGAGATCCTTTTTTCT
TGGGGCTGATACAAGAGCAAAGGATCTAGAGTTCTAGTACTCTAAGCAAGCCTCAAACGGTGCAGGAT
TTGGCCCCAGTGGGCCCACAGGGGCATCTGCCAAAGACTCGTCCATTTCCTAACAGCAGAGCCCAAGC
CAGTAACATGTCCAAAGTCACAGCCCAAAGAGAAAACTGTAAGACACAATCTTGCCTTTCTCCCACCC
CAGGAAGGTACTAGTCTCTGCTCAGTATCTCCCTCCTCTTCTCTCCTCTCCCAAGGCAAAATCACAGG
AAAAGTTCCAGGAGACCATACCTTCCTTCTCCGGAGTCTTCCAACAGGTGCCCCTCTTATTATATGCC
AGCCAGTTGTTTTAAAGGCCATCCATGGGAGGACACCGGCCTCTAGGTCAAGGGAGCTGTGAAGGGAG
ACAGGACTGACAAGGAGCCCAGACAGACACTGTTTAAGATTCACCTGTTCTAGAAAACCTTCCCAGGC
TGATCCCATCTAGCAGTGGGCATTTAAATACCTTCACAGTCTTTAGAAATAGCTTATTGCTAAGGCAG
GTTTTATATAGTATTTCCCTGTTTTTGCTGCTTAGCCATTTTTGTCTTACCGCTTCTTTCTCTGTGGC
AAGGACTATATTTCGTTTCTTCTCTCCACCCTCACTGCCACCTGCTGCTTCACTCTAACCCACTCCCT
GCCTCTTGTCTGCCTGGCTTAAGCTCTCTGATGAAGATATTACACTCTCAGGATAGAATACTGACTAC
CTGATTCCCAGATCGTGTTCTTGACTTGTCTCGAAGTCGATTATCCTTCTTGGAAATCACCCACATCT
TCAACGCTGGCCTTTTCTTTAACCTAGTCTGTGAACTTGCATAGGTCTTGCCCACTTCTGGGTCTTTA
TTATTGTAGCTATAAAATTATTACAATTCTAGCCTCCCCCAGCCTAATCACAATCTGTTCATCGAATT
GACAGCCTGCATTTTGTCTTCATGCAGTTGAAACTGAGAAGGATTTGGAGGAAATTATCTTAAAAGAC
AATTTTTTCTTCTCTATTGTGTTCGTAGAGCTGGGGGTGGGGGTGGGGGAGGAACGCTTATTTTCCAA
GGAATCGGGAGGGGAAAGGTGGAGAGGGCCAAGGGCAGCTAGGAGTGATGTGGGGAGCTGGAGCAGAT
TCGGAAGGACTTTGGGAGCTAATATCTAGGTTTTTGACTCTGAGCCCCTGTTGGGGCTCTCACTTCAT
GGCTTCTCACGCTTGTGCTGCATATCCCACACCAATTAGACCCAAGGATCAGTTGGAAGTTTCCAGGA
CATCTTCATTTTATTTCCACCCTCAATCCACATTTCCAGATGTCTCTGCAGCAAAGCGAAATTCCAGG
CAAGCCTTAGGGAAAAAAGGAAAAACAAAGAAAATGAAACAATTGGCAGTGAAAGGCAGAAAGAGAAG
ATGGAGCCCTTAGAGAAGGGAGTATCCCTGAGTAGGTGGGGAAAAGGGGAGGAGAAGGGAGGAGGAGA
GGAGGAGGAAAGCAGGCCTGTCCCTTTAAGGGGGTTGGCTGTCAATCAGAAAGC
TGGGTCTCCTTGAATGCTGTGCTCGATGTCTCGTAGGAGCGCCGTTCGCC
TCTCTCGTCGCCACCGGATTGTGTTTTTTCGGTGTTGCGCTCTTTTGCGGCTGTGGTCACGAAGCTCT
TACAGGTACGGAGAAACTCATTGAGACTTATTTCAGTAAGAATTATCAAGATTATGAGTATCTGATAA
ATGTAATTCATGCATTCCAGTATGTTATTTACGGAACGGCTTCTTTCTTTTTCCTGTATGGAGCCCTT
CTCCTGGCTGAGGGTTTCTATACAACAGGTGCAGTGCGCCAAATCTTTGGCGATTATAAAACTACTAT
ATGTGGAAAGGGGTTGTCCGCGACCGTTACAGGCGGCCAAAAGGGTCGGGGTAGCAGAGGTCAACACC
AGGCACACAGTCTGGAGCGAGTATGCCACTGTCTCGGAAAGTGGTTGGGTCACCCAGATAAATTTGTA
GGGATTACTTACGCTTTGACGGTTGTATGGTTGCTGGTTTTCGCGTGCTCAGCTGTACCCGTTTACAT
CTATTTTAATACCTGGACGACCTGTCAGTCTATAGCGTTCCCAAGTAAGACCTCTGCATCAATCGGTA
GTCTGTGTGCCGACGCGAGGATGTATGGCGTGCTGCCATGGAATGCTTTTCCAGGGAAGGTGTGTGGG
AGCAACCTCCTTAGTATATGTAAAACTGCCGAGTTTCAAATGACGTTTCACTTGTTCATAGCGGCGTT
CGTGGGAGCAGCAGCAACCCTGGTATCTCTCCTCACATTTATGATCGCTGCTACGTACAACTTTGCAG
TACTGAAACTTATGGGACGGGGCACTAAATTCGACTACAAGGACGACGACGATAAATA
The TPP1/CLN2 protein sequence is:
(SEQ ID NO: 58)
MGLQACLLGLFALILSGKCSYSPEPDQRRTLPPG
WVSLGRADPEEELSLTFALRQQNVERLSELVQAV
SDPSSPQYGKYLTLENVADLVRPSPLTLHTVQKW
LLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGA
EFHHYVGGPTETHVVRSPHPYQLPQALAPHVDFV
GGLHRFPPTSSLRQRPEPQVTGTVGLHLGVTPSV
IRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDS
DLAQFMRLFGGNFAHQASVARVVGQQGRGRAGIE
ASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQ
WLMLLSNESALPHVHTVSYGDDEDSLSSAYIQRV
NTELMKAAARGLTLLFASGDSGAGCWSVSGRHQF
RPTFPASSPYVTTVGGTSFQEPFLITNEIVDYIS
GGGFSNVFPRPSYQEEAVTKFLSSSPHLPPSSYF
NASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSA
STPVFGGILSLINEHRILSGRPPLGFLNPRLYQQ
HGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDP
VIGWGTPNFPALLKTLLNPDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for TPP1/CLN2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
TPP1-DNA (SEQ ID NO: 59)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGCTCCTTTGGGTTCCACTGACACCCCTGCCC
CTGCCCCTGCCCAGAACCAAGTGCCATTTCTCACTCTGGAGCCTTAATAAACTGCAATTTGTATCCAG
TCTCCAGCTTTGTTCTATAGGGATGACTGGAAGACACCTGGCAGAGTATTGTGGATACCTCAGGAGGC
ACAGAGGGGTGGTGGGGTGGGGATGGCACTGGGAGCTCAGGAGCCTAGCCTGAGGCTGATGATCACAT
CTCTCTGCAGCTATTCTTTTCCCTCTAATATGGGCAAAGAGGCCAGCAGGGCCTTGAGAGGGATCAGT
TGGGTGGGAGAGGGGATCTTGGGGATGAGCAGCTCTGGGCCCGAAGTTCTTAAAATAAGTTGGGGTGG
GTACAAGAGCAGTCAAGTGGTTTATTTGTTCTTCTTGGGGGCCACTAAAAATCCACATTGTAAAAAGA
GCTCAATTTGTTGAGCCTTTGTCATGTCAGGCTCTCTGCAGGTGGCTGCCTTGCTTAATCTCAGTGTA
AATTTTCACAGTCATACAAAGGGATTTGGGAACCACTGGTGTTGCCTGTTCTTTGGGGAGCCAGGCTG
TGAGGGAAAGGCAATTGGCCAGTGTTTGAGAAGTTCATGAGATTGAGGAAATTAGAAAAAAAAAAAAA
AGTTGTGGTCAAAGGGAAATGTTTCTGAGCATGATGCTAGTAAATACAGCTCTAGGATCCACGCTTAG
TGGGAAACTGGAGGGATCAATGGACAGAGAGAAGTCAGATTAATAGGAGTGAGGAAAAACAATGGCTT
GAAAAAACAGAAGGTTATAGTCTAAGAAAGCATTCTATAATTATAATTTCAAAGGTAGAGCAGTTTTG
AGAGATAGCAAGCCCAATGCAGCCATGGGACTGGTTTGCTTAAGTGAAGTGAAGGTAATGCTCACTGG
GTTTAATGAGATGAAGAAATGGAAGGTTAGGGTGTTGAATGGGTCTTTTACCTAGATATTTTGATCAT
CTAGGTCAAATGATCGCAGGAGTTGGGATGGACAGAAAGGTGAAGTGCCATAATCTTCAGTGTGGGAA
TATAATCTATAGGTTAATGGAAGCCAGTGGCCTGTAGGACAACAGCAGGAGTAGAGGGATCTATCTAA
AAAGTATTGAGGTCAGAACAAGGGATTTCACATGAGTATTGGATTAATGGTTTTGGAAGTTAAAATGA
CACTGCTGACACCATCTTCCATATGGATTTTTGGGGGGAAAAAAAGGAAGACTGGAAGGGAATTGAAT
CCTCAGGGTTTTAACTCTCATTGAAAATCCTCTTGTAATGACCCCAGTTGGAAGTAGTAAACTCAGAC
CTCCTTGTGGGCTTTGAGTTACCATTAGAAGAAGCAAAGGTCCGTTTCCATTTTATCCACCTGAGCCC
ACTAAACAAGATGCAAGATTCCTCCATGGCCCTTAGAACAAAGTTGATTTCCTTGAAAACCTTGGGAA
CCCATAATAAACAGGACCCCAGCTGATTGTAGATCTCCTGGGAAGCTACTTAAAACTGGAAACTGATT
TGAATAAAAGGATCCTGGTCTTGCAAAAGCTTTACTCTGTTCATAAATGTAGTCGTAAAATGAAGACA
AAATTGATAATATGGGGACATAAAGGATAAAAGAGGAAAAAAATTTTTTCACTGCAATCTTTCGAGGC
AGATCACTTTTATATAAGTCTCCATATTGTAAATGCAGAAACCTAGGCTCTGAGAGGTTATTTTGCTG
ATGTCATACAGCTAGGAAGAACCCCAGTCTGTGGGTCTCTACAGCCCACTCACTTGTGGTGATTCCCA
GGGGACCAGGCTCAGGACGCAGGTGGGGAGCCCTGGGCTTACTCAGTGCTTGACTGGCCAGAGGGGAG
AATCCGGGTGGCGGCCCCACCCTTGCCTAGCATTTGGGACCACCCATGCAAGGGAGGAGCCAGTACCG
TCACTAGTTACTAGGCAGAGGGGTAGTGGTGGTGGAATATAGAGCTCATGTGATCCGTCACATGAC
ATGGGCTTGCAAGCGTGCCTGTTGGGGCTCTTCGCATTG
ATTTTGAGTGGAAAGTGTTCCTACTCACCCGAGCCCGACCAGCGCCGCACACTCCCTCCTGGATGGGT
AAGCCTTGGCCGGGCCGATCCAGAAGAAGAGCTTAGTCTTACTTTTGCATTGCGACAACAGAATGTCG
AAAGGCTTTCCGAACTGGTACAAGCTGTGTCAGATCCGTCTTCACCTCAGTATGGTAAATACTTGACT
CTCGAAAACGTCGCAGATCTCGTACGCCCGTCTCCCCTTACTTTGCATACTGTTCAGAAGTGGCTGCT
TGCGGCTGGTGCTCAAAAGTGCCACTCCGTGATAACTCAAGATTTTCTGACCTGTTGGCTTAGCATCC
GGCAAGCAGAATTGCTCCTGCCCGGAGCGGAGTTCCACCACTATGTCGGTGGTCCTACAGAGACGCAC
GTGGTGAGATCACCTCACCCCTACCAGTTGCCACAAGCGTTGGCCCCTCATGTCGACTTTGTAGGAGG
ACTCCATAGGTTTCCCCCAACTTCAAGTTTGCGCCAGCGGCCAGAACCACAAGTCACTGGTACAGTTG
GACTGCATTTGGGAGTCACCCCCAGCGTCATACGCAAAAGATACAACCTTACTTCACAAGATGTCGGC
TCCGGGACGTCCAATAACTCTCAGGCATGCGCGCAGTTCCTGGAGCAGTACTTTCATGACTCCGATTT
GGCGCAATTTATGAGGCTTTTCGGAGGTAATTTTGCTCACCAAGCCTCTGTAGCAAGGGTCGTTGGTC
AACAAGGACGGGGGCGGGCTGGCATCGAAGCAAGTCTTGATGTACAATACCTGATGTCAGCGGGAGCT
AATATTTCTACGTGGGTTTATAGCTCCCCCGGCCGCCATGAGGGTCAGGAACCGTTTCTTCAATGGCT
GATGTTGTTGAGCAATGAGAGCGCGCTTCCTCATGTCCACACGGTCTCCTACGGAGATGACGAAGATA
GCCTGTCATCCGCATACATACAACGGGTCAACACAGAACTCATGAAAGCCGCGGCCAGGGGCCTCACC
TTGTTGTTTGCTTCTGGAGATAGCGGAGCCGGCTGCTGGTCTGTGTCTGGGCGACATCAATTCAGGCC
AACATTCCCGGCGTCCAGTCCCTATGTCACTACCGTGGGGGGCACCTCCTTTCAAGAGCCGTTCCTCA
TAACCAACGAAATTGTCGACTACATTAGTGGAGGCGGCTTCTCAAATGTGTTCCCCCGGCCGTCATAC
CAGGAGGAGGCAGTTACAAAATTCCTCTCTAGTAGCCCGCATTTGCCTCCATCCAGCTACTTCAATGC
AAGTGGGCGCGCGTATCCCGATGTAGCAGCCCTTTCAGACGGCTATTGGGTAGTCAGTAATCGCGTCC
CCATACCCTGGGTTTCTGGCACTTCCGCCTCAACGCCTGTGTTCGGGGGCATATTGTCACTGATAAAC
GAACACAGGATATTGTCCGGCAGGCCGCCCTTGGGATTTTTGAACCCTAGATTGTATCAACAACACGG
GGCGGGTTTGTTCGACGTAACCCGAGGCTGCCATGAGTCTTGCTTGGACGAAGAGGTAGAAGGTCAAG
GGTTCTGTAGTGGGCCAGGCTGGGACCCTGTAACTGGATGGGGCACCCCGAACTTTCCCGCTCTGCTT
AAAACGCTTCTCAACCCTGACTATAAGGATGACGACGACAAGTA
The ACY2/ASPA protein sequence is:
(SEQ ID NO: 60)
MTSCHIAEEHIQKVAIFGGTHGNELTGVFLVKHW
LENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCD
LNRIFDLENLGKKMSEDLPYEVRRAQEINHLFGP
KDSEDSYDIIFDLHNTTSNMGCTLILEDSRNNFL
IQMFHYIKTSLAPLPCYVYLIEHPSLKYATTRSI
AKYPVGIEVGPQPQGVLRADILDQMRKMIKHALD
FIHHFNEGKEFPPCAIEVYKIIEKVDYPRDENGE
IAAIIHPNLQDQDWKPLHPGDPMFLTLDGKTIPL
GGDCTVYPVFVNEAAYYEKKEAFAKTTKLTLNAK
SIRCCLHDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for ACY2/ASPA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
ACY2/ASPA-DNA (SEQ ID NO: 61)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTTTTTTGGGTCATCCCAAAAATCAAGTACA
CTTTGGGAAACAGGGAGTTAAAAATCTTTCGGAAGTTAACTTGGTATAAGAGTATGAAAAGCCTCTGT
TGCTCTACTTCTGAGGAAATGCTCTCCTTTTTCCTAATAAAGCTTTCCACAGAAGACAAACTCTGTAC
ACAAAAAACAAGGTAAGTATGGGAAATAATTGCTGCAATTCATTAACTCTCAAAAAAGTTATTCATTT
TGACATGTAAGAGAAACTTTATTTATGAATGTGAAATGTGCTTCAAAGTGCTGATCTGTTAAAATTCC
ATAAAACAAGCTTCAAAATGCAAGTCATTTGTGCCAGCTACGAGTAAATAACTGAAGCAGCATTTCCA
GAGAGACTAGGGCAAAGGACAGAACAAACTACAAATCAGCAGAAAAGAAACCAAGCATAGTAGAGTGT
TAATAATTCACCATGGTTACTGCTCTTAAAACCAAAGCAACTAAACAACTGTCATCTGTTTACTTTTA
CGTGTGTTTTCATCATCTCTACACCGTCTGAAGTGTTCAGTGTACATGGATGTGGACAGACAGTCAAA
GCCTACAGGAGCTTTTTTTTTCTATTAGAACAGTCATTTTAATGCATAGATTTGATGTGGTTATTTTG
CTTTCTCTATCTCTGCATTATAAGCTCTTAAAGGAAGAACATTCAGTGGGTTTATTAAATATTAGGAA
GCATTCATATTTTATTTTTCCACCATGTATTTGGTTTGTATGCATGTTTGTTTCCTGAGCACACTGTA
ATGGCTGTTTATGTGAATTCTGAAAGAGCAAAACTAGAACTGTGAAGAAGACCAAAAATAACAGAGAG
GCACCCTATTGTCCTGTGAAAAACACTAGACTTGGGATGAGAAACATGGGTCTCAGGCCTAGGTTCTC
CTACATCCCTGCAGAACCTTAACTGAGTTACTTAACCTCTCTTTCGTTTACCCCTGCAGTGGGGATGT
CAACACCTAACCCACCCTATCGTATAAAATTAATGTATGAATAAACTGAGTGAAAGGACATTATAAAT
TAAACTCTGCAATTGTAATAAATTACTCTTATTGTACCCTCTATCAAACAACCTGGCGTTACTAGTAC
ATGGTATTCCCAGTACTTGAACATATGTGACTTTCTGGGTGACTGAGCATGAAATCAAATCAGATTTG
GCTCAGAGTCATTTCTCCAAAGGGATGTAATCATCTTAGTATTCTGGAAAATTTCCCCTAATAAGACC
CCTTTTTGAGTAACACAGTCCAGTGGAGAGTCCCCGCTGACAGTGAATAAGGCTGTGTCTATGTAAGT
TCACATGATGTGGTTAGCACATGCAGTGTGTCCCAAGACATTTTCAGGCATCACAAAAACTTGAAAAG
TACTAACAGTTGTCTTTCCTTTGGTATTTAGGCAAAAAATGAGGAAGATTCATAAGTAAGTTAACACA
GAATTACCAAAAACCTCATGAGAAAGAAATGAAGGGATGTTTCAGGGTAGCTTTTCGAGTCCCAAGTG
ATCATTGATTTGGCCCTTCTGTTTCTGATTGTGAAAAAGCATTCTGAAAGAATGGGCGCCGGTTCAAG
AGGAGGTCTCTGAGGGTCAGCCTTTGGCTGTTTATAGAGGTGAGATTCAAATGCCCTCAGATCATGAA
AAGTGCTTGAACTCATTTCAGAGAAGAAATGTTTTGAAATGCCCGTGGAAATACTGAGTGGGCCACTT
TTTTATTTTGTGAAATTAGAAACGTATAAACTATTTTTATTATTACAGATAATTGTGAAAGCCTCACT
GGATGACATCCTAGCTGAGGAAAAGAATGGAATTTTTGTATTAGTATGAAATGCTAATTTATTACTGT
ATTTAGATCTACTGACCATCTGAGGGAGTTAGAAGTTAAAGTAAACAGCTGTATCTCTAGTTGATCTT
TGCATATTTTAATCCAAATATGGCAAAGGGCAGGGCTAAAGAAGGGAGTGTCCATAAACGGGGCTC
ATGACAAGTTGTCACATAGCTGAGGAACACATCCAGAAG
GTTGCTATTTTTGGCGGCACTCACGGTAACGAACTGACAGGGGTCTTCCTCGTCAAGCACTGGCTTGA
GAATGGGGCTGAAATTCAGCGAACAGGACTTGAAGTAAAACCGTTTATAACGAACCCACGCGCTGTAA
AAAAGTGCACGCGATATATCGATTGCGACCTTAACCGGATATTTGATCTGGAGAATCTTGGGAAGAAA
ATGTCAGAGGACCTCCCTTATGAGGTGAGACGAGCGCAGGAGATTAACCACCTCTTTGGTCCCAAGGA
TTCCGAAGACTCCTACGATATAATTTTCGATCTCCACAACACGACCTCTAACATGGGTTGTACCTTGA
TCCTCGAGGATAGTCGCAACAATTTCTTGATTCAAATGTTCCACTACATAAAAACATCTCTCGCTCCC
CTTCCTTGCTACGTATACCTCATTGAGCATCCAAGTCTTAAGTACGCAACCACCCGGAGCATAGCGAA
GTATCCAGTGGGAATTGAAGTCGGGCCTCAACCCCAGGGAGTTTTGCGGGCGGACATCCTCGACCAGA
TGAGGAAAATGATTAAGCACGCGCTGGACTTCATACACCATTTTAATGAAGGGAAAGAGTTCCCGCCA
TGTGCCATAGAGGTTTATAAGATTATTGAGAAGGTAGATTACCCTAGGGACGAGAATGGGGAAATCGC
TGCCATCATACACCCCAATCTCCAGGACCAAGATTGGAAGCCACTTCATCCCGGCGACCCAATGTTCT
TGACGCTGGACGGCAAAACGATTCCCCTTGGGGGTGATTGCACGGTATATCCAGTGTTTGTGAACGAG
GCTGCTTATTACGAAAAGAAAGAAGCATTCGCCAAAACCACGAAATTGACACTGAATGCAAAATCTAT
CAGATGCTGTCTCCACGACTACAAGGATGACGATGATAAATA
The MANBA protein sequence is:
(SEQ ID NO: 62)
MRLHLLLLLALCGAGTTAAELSYSLRGNWSICNG
NGSLELPGAVPGCVHSALFQQGLIQDSYYRFNDL
NYRWVSLDNWTYSKEFKIPFEISKWQKVNLILEG
VDTVSKILFNEVTIGETDNMFNRYSFDITNVVRD
VNSIELRFQSAVLYAAQQSKAHTRYQVPPDCPPL
VQKGECHVNFVRKEQCSFSWDWGPSFPTQGIWKD
VRIEAYNICHLNYFTFSPIYDKSAQEWNLEIEST
FDVVSSKPVGGQVIVAIPKLQTQQTYSIELQPGK
RIVELFVNISKNITVETWWPHGHGNQTGYNMTVL
FELDGGLNIEKSAKVYFRTVELIEEPIKGSPGLS
FYFKINGFPIFLKGSNWIPADSFQDRVTSELLRL
LLQSVVDANMNTLRVWGGGIYEQDEFYELCDELG
IMVWQDFMFACALYPTDQGFLDSVTAEVAYQIKR
LKSHPSIIIWSGNNENEEALMMNWYHISFTDRPI
YIKDYVTLYVKNIRELVLAGDKSRPFITSSPTNG
AETVAEAWVSQNPNSNYFGDVHFYDYISDCWNWK
VFPKARFASEYGYQSWPSFSTLEKVSSTEDWSFN
SKFSLHRQHHEGGNKQMLYQAGLHFKLPQSTDPL
RTFKDTIYLTQVMQAQCVKTETEFYRRSRSEIVD
QQGHTMGALYWQLNDIWQAPSWASLEYGGKWKML
HYFAQNFFAPLLPVGFENENTFYIYGVSDLHSDY
SMTLSVRVHTWSSLEPVCSRVTERFVMKGGEAVC
LYEEPVSELLRRCGNCTRESCVVSFYLSADHELL
SPTNYHFLSSPKEAVGLCKAQITAIISQQGDIFV
FDLETSAVAPFVWLDVGSIPGRFSDNGFLMTEKT
RTILFYPWEPTSKNELEQSFHVTSLTDIYDYKDD
DDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MANBA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
MANBA-DNA (SEQ ID NO: 63)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGATTATTCTTTGATGTTCTCTGTTGTCAAA
GTGAAGTAACCTAAATGATGTTATGCTTGCATCCTGGAATGAAAGGAGGAATGAGAATCTTCTATTAT
TGTTTTTCTAAAAATTATATTTCTTAATAAACAGAATATATCCATATGTATCATCAAGGATGAATTTT
CCTCTGATTTGGCTTAATGAAATCTCTGGGAATTATGAAAAAATTCCTTTGCCGCTCTTGTTGCCATA
AACCTTGTGTTATCAGTGTTGCACAGACCATGGCTAGCCATTTAATGCCGTGAATTATGGCATATAAT
TTGAATTGAGAGCTTTGTTTCTATCAAAGGTAAAAATGCTTCTGGAGTGAGTGAGGAAGGCTTTGAAG
CAGTGAGAGCGTTTCCCCTATAGCATCATTGGGCTCTGACAGTAGGACCTTGAAGAGGAGGGTTCTAA
TCCTGTCTGCCACTATGTGACAGGCAAGTCACCTGATCTTTTTTTTTTTTTTTTTTTTAGAGTCTTTC
TCTATAGCCCAGGCTGGAGTGCAGTAGTGCCATCTCGGCTTACTGCAACCTCTGCTTCCTGGGTTCAA
GCGGTTCTCCTGCCTCAGTTTCCCGAGCACCTGCGACTACAGGCACGTGCCACCACGCGCCCAGCTAA
TTTTTGTATTTTTAATAGAGACAGGGTTTCACCATGTTGGCCAGGCTGGCCTCGAACTCCTGACCTCA
AGTGATCCACCCGCCTCGGCCTCCCAGAAGTGCTGGGATTACAGACGTGAGCCACCGCGCCTGGCCCC
GATCTCTTTGAACTCAGTTCCCTCATCTGTAAAGCCAGCGGCTTGGGTTGGATAATCCATACTGTCCT
TTAAGCCAAGATATTCAGGGCTTGTAAATAATGCTGACTTTGCAAAGTAAGATATTGCCCGGTGTCTG
CAGAATCAGGCAATTCCAAGGCCATTGTAAGGCGAAACAAAGCTCAGATTTGATGAGAGAAAATTTCT
TTTCAAGGACTTCTTCCGAAGCATAAATATACGGCAGATAGCGTCAACACAGGAGAAAGGCAGTCTAT
TTTATGCAATGTAAAATTCCGTCTTAACTTCTAGGATTACTGTTACATCCTATTGCAAAAATGGGACT
CAGGTAGACCATTTGACTACAAGACCCGAAATAAGTCAGTGGTATTTCTTGGGTACTCTGGCATTGTT
AGGGACGATCACATATGTTTACTCATTTTATACTTATAACACCTTGAAAACTTCAAGAAACGGAGATG
GAGATTTTGCGGCTTGCCCAGGTCCCACAGCTAGTGAGTGCAGAGGATTTTAAACTCAGCTGCGCGCC
TAGTGCAGGTTCCAGAACCTCAGAAACCTCCGTGGGGCTTTATGAAACATAAGGACGCAGGCCGCTAG
TAACAATAGCTAACGTGAATGCCTTCTCTGGGCCAGGCTCCATGCTGCATGCTATAGTCGCATTTTCT
TGGTTAGCCCTCAGAACAACCTTCTGATGGAGATACTGCTAGTACTTGTTTACTCTTTGAAGGGCGGG
GTAGGCTCTGAGACCCGCGAGTTGAGCTGCAGCGGGGTGAGTGTTACGCTACCAGGTAGACGAGGGTC
TGTGTAAATTTGGCGGAAGGGAAGTGGTGGGTTGTCTCCCAGTTTGGGTTCTCTGAAGGAGTGAGGGG
ACTCTCCAGCTATGGTCTCCACGTACAGTCGGTCTCTGATCTCCCGAGGCTTTGTGCCACTGCGCGCC
CAGGGATCTTTCTGTCCCAATTACCGTGCAAGATTCTTGCCTCCAGTTGTATGTACTGAGGCGGCGGG
AAGAAGCGCCGAGGGAAGGCTCAGACCGCAATGCCCCCCAGCCTGTAGCTATTCTCGGGGGCTGCAGC
TCCCGCACCCGCGACGCCCGGCTTTCAGCGGGTGCAGGCGCAGCCTCCTCGTTCCCCTCCCGCCCGCG
GCTGCGCCCGGAGAGCGCTCAGCTGACCTAGGGGCGGGGCCGGGGCGGGGACCTAAAGCCTCGGCTAC
TTCCGAGGGGG ATGAGGCTTCACCTGCTGCTCCTTC
TCGCGTTGTGTGGCGCGGGTACAACCGCCGCGGAATTGAGTTATTCCTTGAGGGGGAATTGGTCCATC
TGCAATGGCAACGGCAGCCTGGAACTTCCGGGCGCTGTACCGGGTTGTGTGCATTCTGCTCTTTTCCA
ACAAGGGCTCATTCAAGATTCATACTACAGATTTAACGACCTTAACTATAGGTGGGTGAGCCTTGATA
ACTGGACATATTCCAAGGAGTTCAAAATCCCTTTCGAAATATCAAAATGGCAAAAGGTTAATCTCATC
CTTGAAGGCGTTGACACCGTTTCTAAAATACTGTTCAACGAGGTGACTATCGGAGAAACCGACAATAT
GTTCAATCGATATTCTTTCGACATTACTAACGTGGTTCGAGACGTAAACAGCATTGAATTGAGGTTTC
AGTCAGCAGTGCTCTATGCCGCCCAGCAAAGCAAAGCCCATACCCGGTATCAGGTACCTCCAGACTGC
CCTCCTCTCGTCCAGAAAGGTGAATGCCATGTCAACTTCGTGAGGAAAGAGCAGTGCAGTTTCTCTTG
GGACTGGGGTCCATCCTTTCCGACCCAGGGCATTTGGAAAGATGTTCGAATTGAGGCCTACAATATTT
GCCATCTCAATTACTTTACCTTCTCCCCGATATACGACAAGTCCGCCCAGGAGTGGAATCTCGAGATA
GAATCCACGTTTGACGTAGTTAGCTCTAAGCCTGTTGGCGGCCAAGTGATCGTAGCCATACCAAAGCT
TCAAACACAACAGACGTACTCAATCGAGCTCCAACCAGGAAAGAGAATAGTGGAACTTTTCGTTAATA
TTAGCAAAAATATAACCGTTGAGACCTGGTGGCCTCACGGCCATGGAAATCAAACGGGTTACAACATG
ACTGTTTTGTTCGAGCTTGACGGGGGCCTGAATATAGAGAAAAGCGCCAAAGTTTACTTCCGGACCGT
AGAACTTATCGAAGAACCGATTAAAGGTTCCCCGGGCCTGAGCTTTTATTTCAAAATAAACGGCTTTC
CTATCTTTCTTAAAGGCTCCAATTGGATACCAGCAGATTCCTTTCAGGATCGAGTAACATCTGAATTG
TTGCGACTGTTGCTGCAATCAGTAGTAGATGCCAATATGAATACGCTGAGAGTCTGGGGAGGCGGGAT
TTACGAACAAGACGAGTTTTACGAACTCTGTGATGAGCTTGGGATTATGGTGTGGCAAGATTTCATGT
TTGCATGCGCACTTTATCCCACTGACCAGGGTTTCTTGGACTCCGTCACTGCGGAGGTAGCATATCAA
ATTAAAAGGTTGAAGAGTCACCCCTCAATTATAATATGGTCCGGAAACAATGAAAATGAAGAGGCTTT
GATGATGAATTGGTATCACATTTCCTTTACCGATCGGCCAATTTATATAAAAGATTACGTGACGCTTT
ACGTGAAGAACATACGGGAGCTTGTGTTGGCTGGAGACAAGTCCAGACCATTCATCACCAGTTCACCT
ACGAATGGGGCGGAAACCGTAGCCGAGGCATGGGTATCACAAAATCCTAATTCCAATTACTTCGGCGA
CGTGCATTTTTATGACTACATAAGTGATTGTTGGAACTGGAAGGTTTTCCCGAAGGCAAGGTTTGCGT
CCGAATATGGCTATCAGAGTTGGCCAAGTTTTTCCACTCTCGAGAAAGTTAGTAGCACTGAAGACTGG
AGCTTCAACTCCAAATTCAGTTTGCATCGGCAGCACCACGAAGGCGGAAATAAGCAAATGCTTTATCA
GGCTGGACTCCACTTTAAACTGCCCCAGTCCACGGACCCGCTCCGAACGTTTAAAGACACTATATACC
TGACGCAAGTCATGCAAGCACAATGTGTTAAGACGGAAACCGAATTTTACAGACGATCTAGGAGTGAG
ATTGTGGATCAACAGGGCCACACGATGGGAGCTCTGTACTGGCAGCTTAATGACATTTGGCAGGCGCC
CTCTTGGGCTAGTTTGGAGTATGGAGGTAAGTGGAAGATGCTTCATTATTTTGCTCAAAACTTCTTCG
CGCCCCTCCTTCCCGTCGGTTTTGAAAACGAAAACACATTTTATATCTATGGGGTCAGCGATCTGCAC
TCCGACTACTCAATGACGCTTAGCGTTCGAGTGCATACCTGGTCAAGTCTCGAGCCCGTCTGCTCTAG
AGTCACGGAACGCTTTGTCATGAAGGGTGGGGAGGCCGTATGCTTGTACGAAGAACCTGTATCCGAGC
TTTTGCGGAGGTGTGGTAATTGTACTCGAGAAAGCTGTGTAGTGAGCTTCTATCTTTCTGCTGACCAC
GAGTTGCTTAGTCCTACCAATTATCATTTTCTGAGTAGCCCCAAGGAAGCGGTTGGCCTGTGCAAGGC
GCAGATTACGGCGATTATTAGCCAACAAGGGGATATCTTTGTGTTCGACCTCGAGACCTCCGCCGTTG
CCCCCTTCGTGTGGCTTGATGTGGGCAGTATCCCGGGAAGATTCTCCGACAACGGATTCCTGATGACA
GAAAAAACTCGCACAATACTTTTTTATCCATGGGAACCGACTTCCAAGAACGAACTTGAGCAATCATT
TCATGTGACGAGCTTGACGGATATATACGATTATAAGGACGATGACGATAAGTA
The LIPA protein sequence is:
(SEQ ID NO: 64)
MKMRFLGLVVCLVLWTLHSEGSGGKLTAVDPETN
MNVSEIISYWGFPSEEYLVETEDGYILCLNRIPH
GRKNHSDKGPKPVVFLQHGLLADSSNWVTNLANS
SLGFILADAGFDVWMGNSRGNTWSRKHKTLSVSQ
DEFWAFSYDEMAKYDLPASINFILNKTGQEQVYY
VGHSQGTTIGFIAFSQIPELAKRIKMFFALGPVA
SVAFCTSPMAKLGRLPDHLIKDLFGDKEFLPQSA
FLKWLGTHVCTHVILKELCGNLCFLLCGFNERNL
NMSRVDVYTTHSPAGTSVQNMLHWSQAVKFQKFQ
AFDWGSSAKNYFHYNQSYPPTYNVKDMLVPTAVW
SGGHDWLADVYDVNILLTQITNLVFHESIPEWEH
LDFIWGLDAPWRLYNKIINLMRKYQDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for LIPA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
LIPA-DNA (SEQ ID NO: 65)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGTGTATCTAAGAAGCAACTAACTTGCTTTTG
ATTTTACCAGCTAATAGGTGGAAGGGACTTGCCTTGTCTCAGGTGAGACTTTGGACTATGGACTTTTG
AGTTAATGCTGAAATGAGTTAAGACTTTGGGGGACTACTGGGAAGGCATGATTGGTTTTGAAATGTGA
GGACATGAGATTTGGGAGTGGCCAAGGGCAGAATGATATGGTTTGGCTGTGTCCCCACCCAAATCTCA
TCTTGAATTATAGCTCCTGTAATTCCCACATGTTGTGGGAGGGACCCGGTGGGAGATAACTGAATCAT
GGGGGCAGTCTAGCCCATACTGTTCTTGTGGTGGTAAATAAGTCTCACAAGGTCTGATGGTTTTATAA
GAGGAAAATCCTTTTACTTGGTTCTTTCTCTCACATGTGCCGCCATGTAAGACAAGCCTTTTGCCTTC
TGCCATGATTGTGAGGCCTCCCCAGTCCTGTGAAACTGTGAGTCAGTTAAACCTTTTTCCTTCATAAA
TTACCCAGTCTTGGGTATGTCTTTATTAGCAGCATGAGAACAGACTAATACACCTTCTAATTAGTCTC
CCTGCTTCTGTAGTTCAGAATGATCTTTCTAAACTAGATTATGCTGCCCTTCTATTGAAAATATTACA
CTGGCTTCTCATCTTACTCAGAAGACACGGTAAGATCTTGACAAGTGGCTCCCAAGGCACCAGACTTC
TAGGACTTCATGTTCTATTACTTTCTACTATGTACATTCTGTTTTAGCCTCAAAGACCTCACCACTCT
GGCTAGGACCCACCAGGAATATTCCTACCACAGGGCCTTTGTACCTGCTATTTTCACCCAGAATGTGC
TTTCTCCAGTATCTAAGGCTGTTAACTACCTCCTTGCCTGTGCTCAGGTGTCACTTCATAAGAGTCCT
TTCCTGATTACCATATACATATCATCCTCCTTATCCCTGTTTTTTTTTTTTTTTGGGGGATGGAGTCT
CACTCTGTTGTCCATGCTGGAGTGCAGTGGCATGATCTCCGCTCACTGCAACCTCCACCTACCTGGTT
CAAGCCATTTTCCTGCCTCAGCCTCCCAAGGAGCTGGGATTAGAGGCACACACCACCACACCCGCTAA
TTTTGTATTTTTAGTAGAGATGGGGTTTCACCAAGTTGGCCAGGCTGGTCCTGAACTCCTGTCCTCAG
GTGATCCGCCCTCCTCAGCTTCCCAAACTGCTGGGATTACAGGCGTGAGCCACTGTGCCCAGCCCCTT
GTTGTTTGTTGTTGTTGTTGTTTGTTTGTTTTTGTTGTTATTTATAGCACTTATCACCACCTCATGTA
TTATATAGTTATTCATGATGTGTCTCTTCCCATCAGAATATATACAAGAGAACAGGAACCTTGTTTGG
TTGGTTTCTATACCTCCACTGTCTTACTAATGCCTGGCATTTAGTAGGTGCTCAATAAAATCTTTGTT
TTAGAAAATGATTAATAAATAATATGTACATATTGAATATTGTTTCCTCTTTTAACAAATCTTTAATA
ATAATAAAAAATTTAAAGCAGCAAGATTGCTTTGCATCAGGCACAATGATAAGCGCTTTAAATGGAGC
CCATGATTCACTTTCATTTATAGAGCCCACATGCTCTCTGTCAGGCGCAGAAGGTGCCAGCCCTGCAG
GAGCTTCGGGGGCGGAGCAGAAGGCCGCCTAAAACAGCCTTTGCTAAGAGAGCATGCGTAGGCGACGC
GCTGGTAGAGCTGTGGACCTGCCAGCCTGCGAGGCGGAGGACGGGCTCCATCTCTTAGAAACGCCTAC
GGCGCATGCTCTATGGGGTCAACTGGGGGGCTGGCAAGCGGCAGCGCTGGTCTGGGGCGGAGTCTCCG
AGGCACTTCCCGGTGGCTGGCTGCTCTGATTGGCTGAACAAATAGTCCGAGGGTGGTGGGCATCCGCC
CTCCCGACAAGGCAGACCAGGCCCCCTGCAGGTCCCCTATCCGCACCCCGGCCCCTGAGAGCTGG
ATGAAGATGCGCTTCCTTGGCCTCGTAGTTTGTCTGGTT
CTGTGGACACTGCACAGTGAGGGTAGCGGCGGTAAATTGACGGCTGTAGATCCCGAAACTAATATGAA
TGTTAGTGAAATAATCTCTTACTGGGGATTTCCATCCGAGGAGTATCTTGTAGAAACAGAAGATGGCT
ATATACTTTGTCTCAACCGGATACCACACGGACGGAAAAACCACAGCGATAAGGGGCCAAAGCCGGTG
GTTTTCCTTCAACACGGTCTTCTGGCAGATTCTAGTAATTGGGTTACCAACCTTGCAAACTCTTCACT
TGGATTCATTCTTGCGGATGCTGGATTTGACGTATGGATGGGGAACTCCAGAGGGAATACGTGGTCCA
GAAAACACAAGACATTGTCTGTATCTCAAGATGAGTTCTGGGCATTCAGTTACGACGAAATGGCGAAG
TATGATCTCCCAGCATCCATAAATTTCATCCTGAACAAGACTGGTCAAGAACAAGTATATTACGTCGG
ACACAGTCAAGGCACTACTATTGGCTTTATCGCTTTCTCCCAAATCCCGGAATTGGCGAAAAGAATCA
AGATGTTCTTCGCATTGGGTCCGGTGGCGTCTGTCGCTTTTTGCACCAGCCCCATGGCGAAACTTGGG
AGGTTGCCGGATCATCTCATAAAGGACCTCTTTGGAGATAAAGAGTTTCTTCCTCAAAGCGCATTTCT
TAAGTGGTTGGGAACACATGTCTGCACTCACGTGATCTTGAAAGAACTTTGTGGAAACCTGTGTTTCC
TCCTGTGCGGGTTCAATGAACGAAATCTTAATATGTCCAGGGTGGACGTCTATACCACCCACAGCCCG
GCAGGTACGTCAGTCCAGAATATGTTGCATTGGAGCCAAGCGGTAAAGTTCCAAAAATTCCAGGCATT
TGACTGGGGTTCTTCAGCTAAGAATTACTTCCACTATAATCAGAGCTACCCGCCCACTTATAATGTCA
AGGATATGTTGGTTCCAACTGCAGTTTGGAGCGGCGGGCACGATTGGCTGGCGGATGTGTATGATGTG
AATATCCTTCTCACACAAATTACTAATCTCGTGTTCCACGAGAGCATACCAGAGTGGGAACATTTGGA
TTTTATATGGGGACTGGATGCTCCATGGCGGCTCTACAATAAAATCATCAATCTGATGCGGAAATACC
AAGACTACAAAGACGACGATGATAAGTA
The CTNS protein sequence is:
(SEQ ID NO: 66)
MIRNWLTIFILFPLKLVEKCESSVSLTVPPVVKL
ENGSSTNVSLTLRPPLNATLVITFEITFRSKNIT
ILELPDEVVVPPGVTNSSFQVTSQNVGQLTVYLH
GNHSNQTGPRIRFLVIRSSAISIINQVIGWIYFV
AWSISFYPQVIMNWRRKSVIGLSFDFVALNLTGF
VAYSVFNIGLLWVPYIKEQFLLKYPNGVNPVNSN
DVFFSLHAVVLTLIIIVQCCLYERGGQRVSWPAI
GFLVLAWLFAFVTMIVAAVGVTTWLQFLFCFSYI
KLAVTLVKYFPQAYMNFYYKSTEGWSIGNVLLDF
TGGSFSLLQMFLQSYNNDQWTLIFGDPTKFGLGV
FSIVFDVVFFIQHFCLYRKRPGLQAARTGSGSRL
RQDWAPSLQPKALPQTTSVSASSLKGDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CTNS and the 5′ and 3′ UTR sequences are listed below using the same
CTNS-DNA (SEQ ID NO: 67)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG
AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA
CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG
TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA
CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT
GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGAAACTGAGGCACGAAAATCACTTGAACCCG
GGAGGCAGAGGTTTCAGTGAGCAGAGATTGCACCACTGCACTCCAGCCTGGGTGACAGAGCGAGACCC
TGTCTCAAAAAAAAAAAAAAAAAAAAAAGAAGTGCTCTATTTCAGGAGAAACTGGCACTTTCTGAGCC
TACTCTCCCCTAATGCCAGCTCTCCTGCTCACCCCACCAGGGTCAGAGCCAACTTTGCCTCCAATTCA
TAGTCCTTTAAGTAAGAATCCTTTTAATATGCCCTAATGTCCCAACCAAACTAATCTTGAAAGCTTCT
ATGTAGATACAAAGTGCTCCTGAAATCCCTATCCTCAGAAATGCTTCTGAGCCAAATGGGCTCTGAAC
CCTAAACAACCGTGTCCATGTATGTGGCAAGAGCTTGTGAAAAACAAAGCTGGGCCAGGCGCAGTGAC
TCACAACTGTAATCCTAGCACTTTGGGAGGCTGAAGTGGGCAGATCACTTGAGGTCAGGAGTTCAAGA
CCAGTCTGGCGAACATGGCGAAACCCTGTCTCTACTAAAAATACAAAAAGTAGCCGGGCGCGGTGGCT
CACACCTGTAGTCCCAGCTACTCGGGAGGCTGAAGCAGGAGAATCACTTGAATCCAGTTGGCGGAGGT
TGCAGTGAGCCCAGATCACGCCACTGTACTCCAGCCTGGGCAACAGAGCGAGACTTGGTAAGAAAGAG
AAAGAAAGGAAAGAATGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAG
GGAAGGAAGGGAAGGAGTCTCGCTCTGTCACCCAGGCTGGAGTGCAACGGAGCGATCTCGACTCACTG
CAAGCTCCGCCTCCCGGGTTCGCGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCG
CCCGCCACCACGCCCCGCTAATTTTTTGTATTTTTAGTACAGACGGGGTTTCACCGTGTTAGCCAGGA
TGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGCGCTGGGATTACAGGCGTG
AGCCACCGCGCCCGGCTGACCAAAGGTTTCTTGGTCCGCATTCTGCTTCTGTGGAATGAGCCAGGAGC
CAGTTAGGCCTGATTTGACATCTGATTTCCGGAGGAAAACCCAGACTCTGCCCTGGGCAACAAACTGA
ATCCTGAACTTGAGGTCACAGGGCAGGTGTGAGGAGCGGAGAGCAGCAAGAGTGAAAGGGAGGCCTGT
GGTCATTCCATACACACAAGAGATCAGTTCCTCCAAGGTCAGGGGACAGAGAGCACAGGGATCCAGCG
CCAAGCGCAAGGCCCCCAGAAGAAGCCAGAGAGTCGGGGAGGGGGCGGGGGGGAATCGGTCCCAGCAG
GTGGGAAGGATTCTGGGACCAGACCTAAGGGATCATGAGCACAGCTGCTGCAGGCAGACGGGCCCCTG
GAGAAGCTGGGGACAAGCTGGAATAGAGACTTCATTGCGGGAAGGGCTGTCAGGGAGGCCTCCTGGGG
TGGAAAAGGGTGGTCAGGAGGCTCCTGGAGGCGGCGCGGCCCCGGGGGTCCAACTCACCTGGGGCCCG
GCCACCGCGCTCTCGACCGCCGCCTCTGCCCGCGCAGCACGGGCACAGCTCGCCAGCACTGCGAACCC
GGATGGGTCGTCGGGCGCGGCCCTCAGCAGAGCTGCCTTCACAGATGTGGTGCCCAGGTCAATGCCGA
GGGTGATCGGCCGCGCAGCCATTATCTCCCTGACCCGCGCAGCTCCAGTCTGCAGCCAGCGGCCCCAC
AAGTCCGCGCTCTTCGCCCAGGGGGGCGGGGCAGGGGCGGGGAGTCGCCTGCCAATCTTTCAGCCACA
CCCAACATGGAGGCTTCTCGTCTTCCCACTGGCCGGGGAAGGCGAGCTTCCACGCAACCTCTCGGCGG
GCCCCGGCTATAGGCGGAGAGGCGGCGGAAGGCGGGACCTAAAGGGGGCCCCGCCCCACGGGCTC
ATGATCCGAAACTGGCTGACCATATTCATCCTTTTTCCC
CTCAAACTTGTCGAAAAATGCGAGTCTAGCGTCAGCCTCACAGTCCCTCCGGTCGTGAAACTCGAAAA
TGGCTCCAGCACCAATGTGAGTCTGACGCTTAGGCCCCCCTTGAACGCTACCCTCGTTATTACGTTTG
AGATTACTTTTAGGTCTAAAAATATCACTATACTGGAACTGCCTGATGAAGTGGTTGTGCCTCCTGGC
GTCACCAATTCAAGTTTCCAGGTTACCTCACAAAACGTAGGGCAACTTACAGTCTACTTGCATGGAAA
CCATAGCAATCAGACTGGGCCGCGCATCCGCTTCCTCGTTATTCGAAGTTCAGCGATATCAATTATCA
ATCAAGTGATAGGATGGATATACTTTGTCGCCTGGAGTATTAGCTTTTATCCCCAGGTAATTATGAAT
TGGAGAAGAAAATCTGTTATAGGGTTGTCATTTGACTTCGTGGCACTCAATCTTACGGGCTTTGTGGC
ATATTCCGTATTTAACATAGGACTCCTTTGGGTGCCGTATATCAAAGAGCAATTTCTTCTCAAGTACC
CCAATGGGGTAAATCCAGTGAACTCTAATGACGTCTTTTTCTCTTTGCATGCGGTCGTGCTTACACTG
ATCATAATCGTACAGTGCTGCCTTTATGAGCGGGGAGGCCAGAGGGTATCATGGCCTGCAATCGGTTT
TTTGGTCCTTGCCTGGCTTTTCGCTTTCGTTACTATGATCGTTGCGGCAGTGGGCGTAACAACATGGC
TTCAATTTCTCTTTTGTTTTTCTTATATAAAGCTGGCAGTCACTCTGGTCAAGTATTTTCCCCAAGCA
TACATGAACTTTTATTACAAGTCTACTGAGGGGTGGTCCATTGGGAACGTCCTCCTTGATTTTACAGG
TGGCTCCTTCAGTTTGTTGCAAATGTTTCTCCAAAGCTATAATAATGACCAGTGGACATTGATATTTG
GCGACCCGACTAAATTCGGGCTCGGTGTATTCTCTATCGTTTTCGACGTTGTATTCTTTATACAGCAC
TTCTGTCTCTATAGAAAACGCCCTGGTCTTCAGGCTGCCAGAACCGGTAGCGGTTCTCGGCTGAGACA
AGATTGGGCGCCATCTTTGCAACCCAAGGCGTTGCCACAAACAACTTCTGTAAGCGCATCCTCTTTGA
AGGGAGACTATAAAGATGATGACGATAAGTA
The GNS protein sequence is:
(SEQ ID NO: 68)
MRLLPLAPGRLRRGSPRHLPSCSPALLLLVLGGC
LGVFGVAAGTRRPNVVLLLTDDQDEVLGGMTPLK
KTKALIGEMGMTFSSAYVPSALCCPSRASILTGK
YPHNHHVVNNTLEGNCSSKSWQKIQEPNTFPAIL
RSMCGYQTFFAGKYLNEYGAPDAGGLEHVPLGWS
YWYALEKNSKYYNYTLSINGKARKHGENYSVDYL
TDVLANVSLDFLDYKSNFEPFFMMIATPAPHSPW
TAAPQYQKAFQNVFAPRNKNFNIHGTNKHWLIRQ
AKTPMTNSSIQFLDNAFRKRWQTLLSVDDLVEKL
VKRLEFTGELNNTYIFYTSDNGYHTGQFSLPIDK
RQLYEFDIKVPLLVRGPGIKPNQTSKMLVANIDL
GPTILDIAGYDLNKTQMDGMSLLPILRGASNLTW
RSDVLVEYQGEGRNVTDPTCPSLSPGVSQCFPDC
VCEDAYNNTYACVRTMSALWNLQYCEFDDQEVFV
EVYNLTADPDQITNIAKTIDPELLGKMNYRLMML
QSCSGPTCRTPGVFDPGYRFDPRLMFSNRGSVRT
RRFSKHLLDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GNS and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
GNS-DNA (SEQ ID NO: 69)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
TCTTGCCTAGGCTAGATTGCAGTGGTGCAGTCATA
GCTCACTGCAGCCTCGAACTTCTGGGCACAAACAA
TCCTCCCACCTCAGCCTCTTAAGTAGCTGGGACTA
CGGGCATGCACTACCATGCCCAGCTAATTTTTATA
TTTTTTGTAGAGCCAGGGTCTTGCTGTGTTGCCCA
GACTGGTCTCAAACTCCTGGCCTCAAGCAGTCCTC
CTGCCTCTGCCTTCTAAAGTGCTGGGATAACAGGT
GTGAGCCACTGCACCGGGCCTAAAGTCTAAATTCC
TATGTGGCCCTGCATCACTGACTCCTGCCTGCCTC
TCTGACCTCATCTTACCTCACTCTCCCTTTTCCTC
CCTAAGCTGCTTCCATCACCACACTGGCTTCTCTG
TTTCCTCCCAGGTGCCTCTCTCCTTCCTCTGGCAG
CCCTTGTACTTGCTATATACCCAGCCTGAAACATC
TTCTGAATTTTTGCATGACTGACTCCTCATCGCAT
GGCTCTCCGTACTGAAGTTACCTCCTGAGAGGCCT
TTTCTGACCACCCATCTAAAGTAGTTCCCCTTTCT
TCCCACCAGCTGTAATCACATCATCCTGGTTTATT
CTCTTCATAGCACTTACCACCACCTGAAATGACTG
ATTGTTTACCTGTTAGTTGTTTTAAGTCCCCAAGA
GTGCAGAGATCATGAGGGCGAGGACCATCTATCCT
CTGTCCACCACTGCCTAGATTAATGCCTGGCACGT
GTTGTGTTTAATAAATGTTATTACACAGTCTTACT
GTAAATCAGATATTCTTTCATAATTTTACATATTT
ATCAGACAGTTTGACAATTAAGTCCCATACAGTCA
ACTCTGGTCCTTTTCTCCACTTACTCTTTGAATCC
TCATTTCACCTTCAAATGTCCTCACAGTAACTCAG
GTGTTTTATCAAACCAATGTCTCATGAAGCCCAGT
ATTCTTTTCCTGAGGATGGTACCCAGTGATGCTTT
GAGGAGAGTATGGCTGACGACCTTGCTTCGGAAGG
CTGGCGAAGATCTTCTGCTTCTCTAGCGTCTCTTG
GCAGCCTCTTCTGGATCTACTCATGAAATTATCAG
AGCTTTTTTTGGATAAGTTAGAATCCTCATCCTTT
TGAGTTTATGGATTCCGTAGGTTTTGTATTTATAT
AAAACAATGGGGAAAAGTCATTTATACATTATTGA
AAATGAGGCTCCTGTTAACCTACTTATGTATTTAG
ATTAGCAATCTTTAAGGAATTATTGCACAACAAAA
TATACTTAAAACTGCATTCAATATGGTCTTAGGTT
TCAAAGGTATCTCAGAATCATCGTGAACTGACCCA
TATTACAACTAAAATGACCTCTTCAATGGTGCTTT
TTGCTGTCTGGAATCTGAAGAATATTAGTGTTCCT
TTTATTCGTATTTAAATGACTGTCTTCATACTTTT
GTCCTCATTCTAGAAGGAAGTTAATTGTTCTCTGT
ACTTGTAAGGATCTTAGATTTTGAACAAAAGATGA
AAAGCAGGACATAAAATAGTTTCTGAGTAGCCTTT
TGCCTGACAGTGTTCTGTGTACACCTGCTTGCCAC
CTGGTTCAAGTCCTTATCCTGAGGTGCTTGTGGGT
CTATGCAGACAACAGTAGTTGGTAGTTGAACAGTG
TGTGTCTGGCCTCCACCACTGAGTGTGTGAGGTTT
GAATCAGTCTCGGAGTCCTGGGGCCTTGTCTGGCT
TTCAGAATCCAACTGTTGTCTTACTTCTGTTCTAT
AGGGCGGAAGGCTCCCTTTATATCATTTCCCACAT
CCTACTTCTAAAGATTAATTCATGGAGATAGGTCT
GCCCTATCTGCCTTATCTGGGCGCTGATGACTAAT
AAGGGCACAAAGATGTTATTGCCATCAACTGAACT
TTCCCTTCCTGCAAGCATTTTGACTTCCTGCACTT
TTATACAGGATGGAGCTGGCCGGAACCAAACTTGT
CTCTAGAATCATACAAGACTCTCTTTGGCTGTTGC
TTAGAGCTGACCATTTGGGAATAAAAGATTGAGTA
AGATGTAACAAAACAGGAATTCTGGGCTGTGTGTC
TCAATTTATTGGAAGAAATTGTTTAATGGATAATT
ACTTACTTTTAC
ATGAGGCTCCTGCCGCTCGCCCCGGGACGGCTCAG
AAGAGGGTCTCCAAGGCACCTCCCAAGTTGTTCCC
CCGCGCTTCTCTTGCTTGTGCTGGGAGGATGTCTC
GGAGTTTTTGGCGTTGCGGCGGGAACACGACGGCC
AAACGTTGTCCTCCTCTTGACGGATGATCAAGACG
AGGTGCTGGGGGGTATGACACCGTTGAAGAAGACC
AAAGCACTGATAGGTGAGATGGGTATGACTTTCAG
CAGCGCTTATGTTCCGTCTGCCCTTTGCTGCCCTA
GCCGCGCCAGTATCCTTACGGGGAAGTACCCACAT
AATCACCATGTAGTTAACAACACCTTGGAAGGTAA
TTGCTCTTCAAAGTCCTGGCAGAAAATTCAGGAAC
CCAATACCTTCCCGGCCATACTTCGATCTATGTGT
GGATATCAAACATTTTTCGCCGGGAAGTATCTCAA
TGAATACGGTGCTCCCGATGCGGGCGGACTCGAAC
ACGTTCCCCTGGGTTGGAGCTATTGGTACGCACTC
GAGAAAAATTCAAAGTACTATAATTACACCTTGTC
TATAAACGGAAAAGCCCGGAAACATGGTGAGAACT
ATTCTGTCGACTATCTGACGGACGTGCTGGCGAAT
GTAAGCCTCGATTTTCTTGATTACAAGAGCAATTT
CGAACCTTTCTTTATGATGATCGCAACGCCTGCTC
CCCATAGTCCATGGACTGCGGCACCACAATATCAA
AAAGCGTTTCAGAATGTCTTTGCCCCACGAAACAA
AAACTTTAATATACACGGCACCAATAAGCATTGGC
TGATAAGACAAGCGAAGACACCCATGACCAATTCA
AGCATACAGTTCCTGGACAACGCATTCCGCAAGAG
GTGGCAAACGCTGCTCTCAGTTGACGATTTGGTTG
AGAAATTGGTAAAAAGACTTGAATTTACTGGCGAA
CTGAACAATACGTATATCTTCTATACATCTGATAA
CGGATACCACACTGGTCAGTTTAGTCTCCCCATAG
ATAAACGGCAGCTCTACGAGTTCGATATCAAAGTA
CCCTTGTTGGTAAGGGGACCGGGAATAAAACCTAA
CCAGACGTCCAAAATGCTGGTGGCAAACATCGACC
TCGGCCCAACGATTCTGGACATCGCTGGGTATGAC
CTTAACAAGACACAAATGGATGGCATGTCCCTGCT
GCCAATCCTCAGAGGGGCCAGCAATCTTACATGGC
GCTCAGATGTCCTGGTAGAATATCAAGGTGAGGGA
CGGAATGTAACAGACCCTACCTGTCCCAGCTTGAG
CCCTGGTGTATCTCAGTGTTTTCCTGATTGTGTTT
GTGAAGACGCATACAATAACACATACGCTTGTGTA
AGGACGATGAGTGCACTTTGGAACTTGCAGTATTG
CGAGTTTGACGATCAGGAGGTGTTTGTTGAGGTGT
ATAACTTGACGGCAGATCCGGACCAAATTACCAAT
ATAGCTAAAACCATTGATCCGGAACTCCTCGGCAA
GATGAATTATAGACTTATGATGCTGCAGTCATGCA
GTGGTCCCACATGCCGAACGCCAGGAGTGTTCGAC
CCTGGGTACCGGTTCGATCCCCGCCTGATGTTCTC
CAATAGGGGTTCAGTTCGGACGAGGAGATTCTCAA
AGCACCTCCTTGACTATAAAGATGACGACGACAAG
TA
The HGSNAT protein sequence is:
(SEQ ID NO: 70)
MSGAGRALAALLLAASVLSAALLAPGGSSGRDAQAAPPRDLDKKRHAELK
MDQALLLIHNELLWTNLTVYWKSECCYHCLFQVLVNVPQSPKAGKPSAAA
ASVSTQHGSILQLNDTLEEKEVCRLEYRFGEFGNYSLLVKNIHNGVSEIA
CDLAVNEDPVDSNLPVSIAFLIGLAVIIVISFLRLLLSLDDFNNWISKAI
SSRETDRLINSELGSPSRTDPLDGDVQPATWRLSALPPRLRSVDTFRGIA
LILMVFVNYGGGKYWYFKHASWNGLTVADLVFPWFVFIMGSSIFLSMTSI
LQRGCSKFRLLGKIAWRSFLLICIGIIIVNPNYCLGPLSWDKVRIPGVLQ
RLGVTYFVVAVLELLFAKPVPEHCASERSCLSLRDITSSWPQWLLILVLE
GLWLGLTFLLPVPGCPTGYLGPGGIGDFGKYPNCTGGAAGYIDRLLLGDD
HLYQHPSSAVLYHTEVAYDPEGILGTINSIVMAFLGVQAGKILLYYKART
KDILIRFTAWCCILGLISVALTKVSENEGFIPVNKNLWSLSYVTTLSSFA
FFILLVLYPVVDVKGLWTGTPFFYPGMNSILVYVGHEVFENYFPFQWKLK
DNQSHKEHLTQNIVATALWVLIAYILYRKKIFWKIDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HGSNAT and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
HGSNAT-DNA (SEQ ID NO: 71)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
CAAAAGGGTAAAGTTGTTTACCATTCGGACTTTTG
GCCCCCTTCTCCGTGTACAAATTGGTAAAAAGCCT
CAGGATTTTTGAGCTGTCCTTATCCCTCCCCTTGT
TTCTTTTCTTTTCTTTTTTTTTTTGAGACAGGGTC
TCACTCTGTCGCCCAGGCTGGAGTGCAGTGATGTG
GTCTTGGCTCACTGCAACCTCCGTTCAAACGATTC
TCCTGCCTCAACCTCCTAAGTAGCTGGGAGTACAG
GCAGGCACCACCACTGCTGGCTAATTTTTGTATTT
TTAGTAGAGACAGGGTTTCACCATGTTGGCCAGGC
TGGTCTTGAACTCCTGACCTGCCAGGCTGGAGTGC
AGTGGCATAATCTTGGCTCACTGCAAACTCTGCCT
CCCGGATTCAAGTGATTCTCCTGCCTCAGCCTCCC
AAGTAGCTGGGACTACAGGTACTTGCCATGACGCC
CGGCTAATTTTTTGTATTTTTAGTAGTGACAGGGT
TTCACCATGTTGGCCAGGATGGTCTCGATTTCTTG
ACCTCGTGATCCACCTGCCTTGGCCTCCCAAAGTG
CTGGGATTACAGGCGTGAGCCACTGTGCCCGGCCA
TATGTGTTTAATAACCCAGTTTGTCTCTTCTTGCC
TTCAGGACATCAAACGGTCATGCTACTGGAAGCTC
GGACCATGGCCCCTTCTGCTGGGCACCCTTAGATA
GGCCTCTGAGGGAGATCTGATTGCCATTTTCCCGA
AACAGTGCCCCCTATCAGCAGGAAGCAGTTAAGAT
CTGTCTTTGTCCCTATTCTTATCCTAGTGGCAGTT
AGATAGACTTCTTTAGAGCGAGGAATGAGCCAGAT
GGGAAGGGTTCCCTGGTAAAACTCCAACTGGCCTG
TGCACTGCTCTGGGGTGGAGCCACAGAAGTTCGCT
CCTCAGTTTGCAGCTGGGAGGAGCCTGGCCCTCCT
CTTCCTCGGGAGAACCTGGGATTTAATCTGTGAGG
TGGGAAGCCTACAACTAGGAGAACTCTGGCTCTGC
TGAGTCCCTGTTCCCCTTTTTCTTCCTTTACACCC
AATAAAACCCTGCCTTACCCTTCAAATTGTCTGCG
AGCCTAATCTTTCCTGGCGTGTGACAAGGACCTCC
ACCGTCTTTAGCTGAACTAAGGAAAAGTCCCGCAA
CATTTTCATGTGTGCCTTTGTATTTTTATTACATA
TATGGATGTCCCTAAACAACATACATTATTGTTTT
GCTTTATATATTAAAAAGGCATTCTGCAATTTGCA
TTTTCCCCAGCCTTGTGTTTTGAGATTTATCCATG
TGGATGCGGGAAGCTGTAGAGCACTTCCCCTGCTG
TGGGGCAGTTTGTTTTCTCGCTGGCGGACATTCAG
CTTGTTGACAAGGTTTTGCAATTACAAGCACCTCT
GCTATAGGTATTACTGTACCTGTCCCTTATACCTG
CGATAGTGTCTCCCGGCATACAGCCAAGAATGGGT
GTGCACACTCCTCGACCTGCTCCCTTCCACTTCGT
CAGCCTGGCCGGGGGCTCTTTCAAGAGGTGGGGCC
GCTTGGTGGCTTCTAAGTCGTGCCTCTCCCTCTGG
GTAATAAACGCCTTGGGGGCAGGGACTTTGCAGTC
TTGCTTATTGAGGCGTTTTCCAAAACAGGGACCGA
GGGCTCTAACACCCGTGCGGAGGGTGGCCGGCGGG
GGCGGGAGTTTGGCAGAATGCGGCTGGAGAAGGTG
GGGCGAGGGAAGAAGGCTCCTGGCCTGCAGGGGCC
TCTCTTCCGGCTGTTTTTCCTCCCGAAGACAAACA
CTCCCAACGCAGGGGCGCAGAGCCTCGGCTTCTTT
CCTGGCCAGCTCCCTCAAGGCAGGGCCTAGCATGG
CCCGGCCCAGCCCCTAGGTTCCCCCGCCCGCGGCT
CCCGGGCGCCTCCGCCTCCCGCGGTGACTCAGGCG
GCGGTGACGGCAGCGGAGGGGGCGATGACGGGCGC
GCGGGCGTCCGCGGCGGAGCAGCGCAGGGCGGGGC
GCAG
ATGAGCGGCGCGGGCAGAGCTTTGGCGGCCCTTCT
TCTGGCGGCATCTGTGCTTAGTGCAGCACTCTTGG
CTCCTGGGGGAAGTAGTGGTCGAGACGCTCAGGCC
GCGCCACCGAGAGATCTGGATAAGAAACGGCACGC
AGAGCTCAAGATGGACCAGGCACTTCTGCTCATAC
ACAACGAATTGCTTTGGACCAATTTGACGGTATAT
TGGAAGAGTGAGTGTTGTTACCATTGTCTCTTCCA
GGTTCTTGTGAACGTGCCACAGAGTCCTAAAGCTG
GGAAGCCTAGTGCTGCGGCGGCATCTGTTTCTACA
CAGCATGGTAGCATACTGCAACTTAACGACACTCT
GGAGGAAAAAGAGGTATGTCGATTGGAATATAGAT
TTGGCGAGTTTGGCAATTATTCATTGCTGGTTAAA
AATATCCACAACGGTGTTAGCGAGATTGCATGCGA
TCTCGCTGTTAATGAAGATCCGGTCGATTCTAACC
TGCCGGTCTCAATAGCTTTTCTGATAGGGCTGGCA
GTGATTATCGTAATCTCATTCTTGAGGTTGCTCCT
CTCACTCGACGATTTTAACAACTGGATCAGCAAGG
CAATTAGTTCCAGAGAAACTGACAGGCTCATTAAC
AGCGAACTTGGTTCACCCAGTCGCACAGACCCCCT
TGACGGCGATGTGCAACCTGCGACATGGAGATTGT
CCGCCCTCCCTCCGCGACTGCGATCAGTGGATACC
TTCAGAGGAATTGCGCTCATTCTTATGGTTTTCGT
AAATTACGGAGGGGGTAAATACTGGTATTTTAAAC
ATGCCAGTTGGAATGGACTCACCGTTGCAGATCTC
GTGTTCCCGTGGTTCGTCTTCATTATGGGCTCATC
CATTTTTCTCAGCATGACCTCCATCCTCCAGCGAG
GATGCTCCAAATTTCGCCTCCTCGGAAAGATAGCC
TGGCGAAGTTTCCTGTTGATTTGTATTGGGATTAT
TATCGTAAACCCCAACTACTGTCTGGGGCCTTTGT
CATGGGATAAAGTAAGGATACCTGGAGTTCTCCAA
AGACTCGGCGTGACTTATTTCGTCGTTGCAGTTCT
CGAACTCCTCTTTGCCAAGCCGGTCCCCGAGCACT
GCGCATCAGAACGCTCATGCCTCAGCCTTCGCGAC
ATAACAAGCAGTTGGCCTCAGTGGCTGCTTATCCT
TGTCCTGGAAGGCCTTTGGCTTGGTCTTACCTTTT
TGCTTCCCGTACCAGGATGCCCAACTGGCTACCTC
GGGCCCGGAGGGATCGGCGACTTTGGAAAGTATCC
CAATTGTACCGGAGGAGCCGCGGGCTATATTGATC
GACTTCTCTTGGGGGATGACCATCTTTACCAACAC
CCGTCTAGTGCAGTACTTTACCATACCGAGGTAGC
CTATGACCCGGAGGGAATCCTTGGTACCATTAACT
CAATAGTCATGGCGTTCCTTGGTGTACAGGCTGGA
AAAATTCTCCTTTACTACAAAGCTCGAACGAAGGA
TATTCTTATAAGATTTACAGCGTGGTGCTGCATCC
TTGGACTGATTTCTGTGGCCCTGACGAAGGTATCC
GAGAACGAGGGATTCATCCCCGTTAATAAGAATCT
GTGGAGCCTTTCCTATGTCACCACGCTCAGCTCTT
TTGCTTTCTTCATTTTGCTTGTTCTCTATCCAGTA
GTGGATGTAAAGGGCCTGTGGACAGGGACTCCGTT
CTTCTACCCGGGGATGAACAGCATACTTGTTTATG
TGGGACATGAAGTATTTGAAAACTATTTCCCCTTT
CAATGGAAACTTAAAGATAATCAAAGTCACAAAGA
GCACTTGACACAAAACATTGTAGCGACAGCGTTGT
GGGTCCTCATTGCATATATCCTCTACAGAAAGAAG
ATATTTTGGAAGATAGACTATAAAGATGATGATGA
TAAGTA
The NeuroD1 protein sequence is:
(SEQ ID NO: 72)
MTKSYSESGLMGEPQPQGPPSWTDECLSSQDEEHEADKKEDDLETMNAEE
DSLRNGGEEEDEDEDLEEEEEEEEEDDDQKPKRRGPKKKKMTKARLERFK
LRRMKANARERNRMHGLNAALDNLRKVVPCYSKTQKLSKIETLRLAKNYI
WALSEILRSGKSPDLVSFVQTLCKGLSQPTTNLVAGCLQLNPRTFLPEQN
QDMPPHLPTASASFPVHPYSYQSPGLPSPPYGTMDSSHVFHVKPPPHAYS
AALEPFFESPLTDCTSPSFDGPLSPPLSINGNFSFKHEPSAEFEKNYAFT
MHYPAATLAGAQSHGSIFSGTAAPRCEIPIDNIMSFDSHSHHERVMSAQL
NAIFHDDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NeuroD1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
NeuroD1-DNA (SEQ ID NO: 73)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
TGTCGCGAACTGGAGGTTTCTGCTTTCTGGGGGTG
AGGACAAGGATTTAGCAGAGGGACCTCTAGGCTAC
CCCTGACCTCGAAGCTAGCTGGAGTCCTTTCTCCC
ACTCCGTCCCCAGTTCTCCTCCGGAACTCCCCAAA
GTTGGAAAAATGAGAGCCTAGGCACGAGTTGCATA
TGCCTGCGGCATAGTGTGCTGCCAGTCGGGGCAGC
TGCCGGGTGAGGGGCAGTACTTAACCTGGCCCTGC
CGCAAACGTCGGGCTGTGTACTATCTTCTAAGGGC
TAGTACTCCGACGCCCTCGAGTTTTAGCCCAACAC
TGAAGATACAGACAGTACAGGGGTAAATCCTGGGC
CCAGGCTCCTGGGTGAATTATTTTATCCTCCCCTA
TGCGCTTTGTCAGCCAAGTGAATGTAGAAAAGCAA
GCAAAACTCCAGAACCCCACAACGATTCACGCCAC
GCTTCGGTGGCACAACTCTTTTCTTCCCCTTTTAG
ATTAGTACTGTGCAGGGAAGGCTGCACCTGCTACC
TTCAGACACCGGGGATCTGGCTAGGACCCTCTTCC
TCTACCCCTACTCTCTCCTCCCGTCCCCACCCTCT
CCCAGATGCACCCCAATCCAGCCTCTCAACCCTGT
CGCTGTTTGCAAACTCGAGGGATGTTTAGTGCAAT
TGCCTTTAAATAAGCAATTCACGTAAGAGGTATTT
ATTGCAGAGGGTTTCAGGTCTGGGAGGGGGTAAGG
AGTTAGTTAATGAAGGATTAGAGGCAAAGCTGGGA
AAGAACGAGTAGACAGGCCAGTTTCTTTCTTTCTT
TTTAAAATCTATTATTCTGGAAAACCCTTGTTCGA
AAAGAGTAAAGAATTGCTATTTGGGCAACAATATG
GCTCCTTCAGAACTGGTCGAGAATTTCTGTGGTCT
TTGCTTGACCTTCAAGTTGGGAGTTTCAAATCAGA
GGCTTTGAAGTCTGGAGGAGTTCGCAGCCATTAAT
CCTTCCGGGGTTGTGCTAAAGGCGTTTCTAGAAAG
AGATCGGAAAGACCCGTTCAGCACAGGCCCATTGC
ATCTTCTCTTTGAAAACGCTTGTCTGAATCAAGTA
TCTTATACAGACCCGAGACTGAGGGGAGCAAGAGC
GCAGGTCCGGCTGTGGCGAGGTGTCCACCACCGTA
CTTGTGGTCAATGCCTGGACTAGAGAGCCGAGGCC
GTCCAGGGCGGGCTGGCCAGGGAACCAGAAGCGTC
CCTGGACTGGCTGAGTGAGGGTGCCCTTTCCAGCA
ACCCAGTGGCCATGGTTAAAAGGCAGAATACAACC
GTCAAAGAAGTCCCCAGCTCCCACATAAGAGAGCG
CAAAGGCCAATGGAACCAAGGCCTCCTCGCGAGAA
CTAGCTCGCTTTGAGGACAAGATCCTGGGGATGGA
GGTGGGGACTGACGTAGTGAGAGGGTCTGGAGGAA
CAGTCGTAGCTGAAGGTCAGGACATGAAGAATTGC
ACGTATGGTAGGGATAGAATGGCAGGTACAACTTT
TCTGTACTGAAGGAACTGGGAGAGGACGATCCGGT
TAGGGAGGTTGGGGAACTAATCTCAACGCTGCGTT
TACAGATGAAGCCGCTTTTATATGGCGTATATGTT
TGCTTAGAGGGGCCGACGGAGATTAGGAGAAGCCA
TCCTTTGGCGCCAATGATCAAAGCGTCTGCCAAGG
AGAAGAAGCCAAGGGATGGGCCTTTCAGAGAGGGC
AAGGAGTCATGCTGCTCTGGATGCCAGTGTCAGGA
CAAGAAATCGAAAGGAGCGAGGACTCTTCACTGCG
TGCCTCAGTCTCCCCGCTTCTGCCTCTTTCACCTC
TGTCCTACTTCCGGCGCGAAAGCAGGCCACTCGCT
CTGATCTAGACCTAGTTAACATTAGCTTTTCCCTT
CCTTCCCTCAAATCCCCTCCCCCCTCTATCCCCGT
CCCTTCTGCCGCCTGAAAGGGTTAATCTCTCCTGC
GGGTAAAAACAGGTCCGCGGAGTCTCTAACTGGCG
ACAGATGGGCCACTTTCTTCTGGCCACAAAGGGGC
CGGAATGGAGCGCTCCGCGGCATACAAATGGGCAG
GTCACGTGGTTCCAGGCTCTTGGCTGGACCGGGAA
GACCATATGGCGCATGCCGGGGAGGAAGGAGGAGG
GGCGGGGGTAGGGGTGGAGGGTGAGGGGAGCGGTT
GTCGGAGGAGGGCGGGAGACGAGCAAGGCGTGGGG
AGAAGTGGGGAGGAGGGGAGAACGGGGAGCGCACA
GCCTGGACGCGTGCGCAGGCGTCAGGCGCATAGAC
CTGCTAGCCCCTCAGCTAGCGGCCCCGCCCGCGCT
TAGCATCACTAACTGGGCTATATAACCTGAGCGCC
CGCGCGGCCACGA
ATGACGAAAAGCTACAGCGAGTCAGGGTTGATGGG
GGAGCCTCAACCCCAAGGGCCCCCATCTTGGACGG
ATGAATGCCTGTCATCACAAGACGAGGAACACGAG
GCAGACAAGAAGGAGGACGACCTGGAAACGATGAA
CGCTGAGGAAGACAGCCTCAGGAACGGAGGCGAAG
AAGAAGATGAAGACGAAGACCTGGAGGAAGAGGAG
GAAGAAGAGGAAGAGGATGACGACCAGAAGCCCAA
ACGGCGCGGGCCCAAAAAGAAGAAAATGACTAAAG
CCAGGTTGGAGCGGTTCAAACTCAGGAGGATGAAG
GCTAATGCAAGAGAGAGGAATCGCATGCATGGACT
CAACGCCGCTCTCGATAACCTCCGGAAGGTCGTGC
CATGTTATTCTAAAACACAAAAACTGTCCAAAATC
GAGACCCTGAGGTTGGCAAAGAACTACATATGGGC
GCTCAGCGAGATTCTTAGATCTGGTAAGTCTCCGG
ACCTCGTTTCCTTCGTCCAAACCCTGTGTAAAGGT
CTGTCACAGCCAACCACCAACCTTGTAGCTGGGTG
CTTGCAGTTGAACCCCCGCACTTTCCTTCCTGAAC
AAAATCAGGATATGCCTCCGCACCTCCCTACCGCC
AGTGCATCTTTTCCGGTACATCCCTACTCATACCA
AAGCCCGGGTCTGCCTAGTCCGCCGTATGGTACAA
TGGATTCCTCCCACGTGTTCCACGTAAAACCCCCA
CCTCATGCCTATTCCGCTGCCTTGGAGCCTTTTTT
TGAGTCTCCGTTGACAGACTGCACCAGTCCTTCTT
TTGATGGGCCCCTGTCACCTCCTCTTAGCATCAAT
GGAAACTTCTCTTTCAAACACGAGCCAAGTGCAGA
GTTCGAGAAAAATTATGCTTTTACTATGCACTACC
CCGCAGCTACCCTGGCAGGTGCGCAAAGTCATGGA
TCTATCTTTTCAGGAACGGCTGCGCCGAGGTGTGA
GATACCCATTGATAATATCATGAGTTTCGATAGCC
ACAGCCATCACGAGCGCGTGATGAGCGCTCAACTG
AATGCAATTTTTCATGACGACTATAAAGATGACGA
CGATAAGTA
The SLC17A5 protein sequence is:
(SEQ ID NO: 74)
MRSPVRDLARNDGEESTDRTPLLPGAPRAEAAPVCCSARYNLAILAFFGF
FIVYALRVNLSVALVDMVDSNTTLEDNRTSKACPEHSAPIKVHHNQTGKK
YQWDAETQGWILGSFFYGYIITQIPGGYVASKIGGKMLLGFGILGTAVLT
LFTPIAADLGVGPLIVLRALEGLGEGVTFPAMHAMWSSWAPPLERSKLLS
ISYAGAQLGTVISLPLSGIICYYMNWTYVFYFFGTIGIFWFLLWIWLVSD
TPQKHKRISHYEKEYILSSLRNQLSSQKSVPWVPILKSLPLWAIVVAHFS
YNWTFYTLLTLLPTYMKEILRFNVQENGFLSSLPYLGSWLCMILSGQAAD
NLRAKWNFSTLCVRRIFSLIGMIGPAVFLVAAGFIGCDYSLAVAFLTIST
TLGGFCSSGFSINHLDIAPSYAGILLGITNTFATIPGMVGPVIAKSLTPD
NTVGEWQTVFYIAAAINVFGAIFFTLFAKGEVQNWALNDHHGHRHDYKDD
DDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SLC17A5 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
SLC17A5-DNA (SEQ ID NO: 75)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
GTCAAACTAAGCAAAGGGTATGGAGAACTCACTGT
ACTATCTTTGCAACGTTTATGTAAACCTAAAATTT
CTAAAATAAAAAATATTAAAAAAAAGAATTCCTCT
GGTTTGAAGTCTTTCAAGTCTGTTGCAACTATATT
CCCTGGCCCAAGTTATCTATAACCTTGGTCATCTG
GGAGCTTGTTAGCAATACAGAATCTCAGGCACATC
CCAGATGTACTGGGCTTCTCAGAGAAACAGCCCCA
ATTGGGTAGTTTGGGTAATAAAGTTTTGGCTTTCA
CAATATAGGCTGGCCAACTCGACCCAAAACAGATG
ATGGTGCACATGCCTGGAGACCCAGGAGGACCTGT
GGTGCAGATGAAGTCTGAGGACACTCTGCTGGAGA
AGTCTCCCTTGCTTGGGCAAGAGAAGTGGGGGAGT
CGGATTTTTTATTCTAGATAGGCCTTCAACTGATT
GAAGGAAGCCCACCCAGATTATGGAAGGCAGCCAT
CTTTACCCAGAGTTCAATGATTTTAGTGTTAACCT
CATCCAAAGACAACCAGCAAGTTAACACATAAAAT
TAACCATCACACCAGATCTGCTGAATCTGAATCTA
CATTTTAAAAGGATTTGCCAGGTGACTCTGCATAA
TCCAGTTTGAAAATTGCATTTTTCTACAACCCTTA
GAGAGTGTAAAAATCTACATGGTAATTCAGTAACT
CAGAAACAAGGCTTGATTTGCTGCTTTAACTTGAG
AACTTTTCTAGCATTTACTGATCTGGAGGTAGGGA
TGCCTACAGAAATCCTCGCCCTCCCTTCTAGGTAA
AGGACCCTCCCCTTTGTTCTCACGTGAACCTCACT
AAGCTTCTAACCTGGTTTACTGAATTAGTGGCTTG
TGGGTCTTCCCTGTCTACACCAAACTCTCCGAGAG
CATCTACATCTTATTTTCTACCTCCACAGAGACAG
CCTTTATTGGCGGATCCAGATCTGCCCTGCCAAGG
CAAGCTGGGTTTTCCTAGTTTCACTTTCAGAGTCC
GCAAATGCTAGCACAATCTATCCAAATTCTATCGT
GGAGATAAAGCATGCACACATACATCAGAGGATTC
CATAGGTCGAACCATATGAAACTACCTATGTTGAT
TACTTTTACCTATAAAACCAGCAACATCATAGGAC
TCAACAAATTTCCATTGCTGTTTTTCCGCCTAAAA
GCTATTTTAGGACCAGGAGCAGTGGCTCACGCCTG
TAATCCCAGCACTTTGGGAGGCCGAGGAGGATTGC
TTGAGCCCAGGAGTTCGAAACCAGCTTGGGCAATA
TAATAAGACCAAGCCTCTACAAAAATAAAAAGTAG
AAACAAAATTAGCCAGATGTGGTGGCATGCTCCTG
TAGTCCCAGCTACTTGGGGGAGCTGAAGAGAATCG
CTTGAGTCCAGGAGTTGGAGGTTGCAGTGAGCTGC
GATTGCGCCACTGCATTCCAGCTTGGGCAACAGAG
CAAGACCCTGCCTGGGAGAAAAAAAAAAAAAAAAA
AAAGCTATTTTAGGGACAATATGCCGCCACAGTCA
CGAGGTAAATATGCCGCCACAGTCACGAGGTAGAT
CGTACAAAGGTTGCTAACAGTATGGCAACTGACCG
CTAACAAGCGAATGTCAAGTTGTGAAATGCACACC
ACCCACTTCCCTAGTTCGGTCGAAGCCCTCCCCTT
AATTATGTGCAATTCAAGTCCCCACTGCCCGCCCG
CAAGCCCCCACTCATCCTCGCTGCGGGCAGGGTGG
CCCCTGCACTTTACAAGGGGGTGCAGGAGCGGGAG
ACGGTCGTCCGAACACCGGCTCCCCGGCATGCGTA
GACCGGCGGGCGGAGCGGGCTCACTTTGCGCCAAT
CCTACGAGAACTCCCAGAACTCCGCTTCCCTAGTC
CAACCCAAGCCAGAGTTGCCCACACCTAAGATGGC
GGCGGGGGCGGAGTCGGCGCGGCCGCCTCTGGGCG
GGACCGCGGGGACTAGACGTGGCCGCGGGGCGGTGT
CAT
ATGCGGAGCCCCGTGAGAGACCTGGCCAGAAACGA
TGGGGAAGAGTCTACAGACCGGACCCCGTTGCTTC
CGGGTGCTCCCAGGGCAGAGGCCGCCCCTGTCTGT
TGTAGCGCACGCTACAACCTCGCCATACTTGCTTT
TTTCGGGTTCTTCATAGTTTACGCCCTGCGGGTGA
ACCTTAGCGTAGCTCTTGTAGATATGGTCGACTCT
AACACTACTCTGGAAGACAACAGAACCTCTAAAGC
GTGTCCAGAGCACTCAGCCCCTATTAAGGTACACC
ATAACCAAACCGGAAAAAAGTATCAGTGGGACGCG
GAAACCCAGGGGTGGATACTCGGCTCATTTTTCTA
CGGTTATATTATCACCCAGATTCCTGGAGGCTATG
TAGCCTCCAAGATCGGTGGGAAAATGCTCTTGGGA
TTCGGCATTTTGGGTACTGCGGTACTTACCCTGTT
CACTCCTATAGCAGCCGATCTTGGGGTTGGCCCAT
TGATCGTTCTCAGAGCCCTCGAAGGTCTGGGAGAG
GGCGTTACATTTCCAGCAATGCACGCGATGTGGTC
AAGTTGGGCGCCACCCTTGGAGCGAAGCAAACTTC
TCTCCATTTCATATGCAGGGGCCCAGCTGGGAACT
GTAATAAGTCTGCCGCTGAGCGGTATAATCTGCTA
CTATATGAATTGGACATACGTCTTTTATTTTTTCG
GAACAATAGGGATTTTCTGGTTTCTCTTGTGGATA
TGGCTGGTTAGCGATACCCCGCAGAAGCACAAACG
CATAAGTCACTATGAAAAAGAGTACATCTTGTCTT
CACTTCGCAATCAACTGTCTTCTCAAAAGAGCGTG
CCTTGGGTACCGATATTGAAGAGCCTGCCTCTCTG
GGCAATCGTAGTAGCGCACTTTTCATATAATTGGA
CCTTTTACACACTGTTGACTCTTCTCCCAACGTAT
ATGAAGGAAATTCTCCGATTTAACGTGCAAGAAAA
TGGATTCTTGTCATCACTTCCTTACTTGGGTTCAT
GGCTCTGCATGATTTTGTCTGGTCAGGCGGCCGAT
AATCTGCGCGCCAAATGGAACTTTTCTACCTTGTG
TGTAAGACGAATCTTTTCCTTGATCGGCATGATAG
GCCCCGCTGTGTTTTTGGTAGCAGCCGGCTTCATT
GGGTGCGATTACTCACTGGCTGTCGCGTTTCTCAC
AATTTCTACCACACTTGGCGGTTTTTGTAGCTCTG
GCTTCAGCATAAACCATCTCGACATAGCACCTTCC
TACGCGGGTATACTGTTGGGTATCACAAATACCTT
TGCCACAATCCCAGGTATGGTCGGCCCAGTTATAG
CCAAATCTCTGACTCCTGACAATACTGTAGGAGAA
TGGCAAACAGTATTCTATATCGCCGCTGCTATCAA
TGTTTTCGGGGCAATTTTCTTCACGTTGTTCGCGA
AGGGGGAAGTCCAAAACTGGGCTCTTAATGACCAT
CATGGGCACAGGCACGACTACAAGGATGATGATGA
TAAGTA
The CLN6 protein sequence is:
(SEQ ID NO: 76)
MEATRRRQHLGATGGPGAQLGASFLQARHGSVSADEAARTAPFHLDLWF
YFTLQNWVLDFGRPIAMLVFPLEWFPLNKPSVGDYFHMAYNVITPFLLL
KLIERSPRTLPRSITYVSIIIFIMGASIHLVGDSVNHRLLFSGYQHHLS
VRENPIIKNLKPETLIDSFELLYYYDEYLGHCMWYIPFFLILFMYFSGC
FTASKAESLIPGPALLLVAPSGLYYWYLVTEGQIFILFIFTFFAMLALV
LHQKRKRLFLDSNGLFLFSSFALTLLLVALWVAWLWNDPVLRKKYPGVI
YVPEPWAFYTLHVSSRHDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN6 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
CLN6-DNA (SEQ ID NO: 77)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
AAAGGCAGATGTGTTTGTATTTAAGAGATTGGAGG
ATTAAATGAGCTAGAGAGGCTCCCTCCACACGGCC
TCATCCTCTGATGGCTGGAAGCCCACCTCTGAGTG
TTATTAAATCGATGATGACATCATGGGCACTGCAT
GCCCCTCCCTCTGGAGCCCAGCAGGCTTGCAAAGC
CTGCAGAGGATAAGAAATTGGGGTCAGAGCGGGAA
GCCTCAATCCTTCTTCTCTGGTGTATACCGAGATC
GATGTGTAGATCAGATTCACCAGAATTAAATCTGG
GGCCCCGTCTGAGTGCTGTCCTTGGCTGACCCTTG
GGCACAGTACTTCAGCTCAGGGCCTAGGTTTTTCT
CTGCTACAAAACAGAGACAATCACCTGTTCTCCTT
ACGACCTGGTGTGTGTGGATCAAATGAAACAAGGA
AAGCTTTAAAGCAAATGTGTTCTTCAGGGGACCAG
GGGCGGAGGGGGGGGATTGAGGTGTGGCCTGTGGG
CTGCTAGAGCCCAGGATGGGGCTGATGGAAAATGA
CTCCCAGGCAGGCAGTCCTAGCCTCCCACAGCCAA
GAAAGGACATGCAGGTTCTGACCAAAGGGGAAAGA
AATAAATCCAATAAACATCTCCCAAGAAGAAAGAC
AGGAAAGAAAATAGAATGGAAATAGGCATAGCTCA
GACCCCTCATGGTCTGGGAAGCAGACCAAGGATAC
TGGGCAGGGGAATGGCACATTGCATTTGCATCTGA
GGCACATCCCTTCCAAGAGGCACATCCCTTCTGCA
GCGGCTTGAGGGCTGGGTGAGAGGAGACAGGACTG
GAGACCTGCACATGTCGTGTGCGCCTGGTGTAGCA
CGGGGGTGGTGGGGAGAATGGGAGTTGGTTGCAGT
TGTTCTAGTTAGCGGCCTGGGCTGCTGACAGTGAC
CGTGGGGAGGAGAGAGTTTGTGACATTGACAGTGG
TGTGGAAGGTAACCTTTCTGTGGAGGGAAACCTCA
GGTCTCGAGACGGGCTATTGTAAATAACTTAGTCC
ACCAGTGCTGGGCTCTCTGCTAAGAGTTTCATATA
GTCATCACAACTCCAATGTAGTAGATGCAATAGGC
ATCTTCTTGTTACAGATGAGTAAACTGAAGCTGTG
AGGGGTTGAGCCATTTGCCCGCATCACAGCTAGTT
CAAAGTGGTACCACTAATGAAGTCCTGGCAATCTG
CCCTGCAGGCTGTTCTCAGGTTTGACCTTTGGTTC
TGTTTTTCACTTGAGGATGCTGTCCCCTTAGGTTC
TGTCTGTCTTGTATGCTCCGGTGACTCACGAGCCT
GTCCACTGGGTTCCCAGGTCTCGCCTCAGCTTCAG
ACCACCGGTCCAACAGCCTTCCTGACCCACCTCAA
GCTTAATGCGTTCAAAGATGAATCTTTATTTACAC
GAAATCTGCTCTAGCCCACTTCCCGGGGGGTGCCT
CCACTATCCACCCAGGGGCAGAATCCGGCCACTGC
CTGAACTCTTCTCCCCTCACCCCCCACATCCAGAG
TCCCAGTCACCATACCTCTCACACGACTCTAGATG
TCACCAACTCGCTCCTTCCCACTGTCACCGCCAGC
CCCTCACTAGAACATCTGCAACCCACGTGCTGCAC
CACGCGGGTGCTACACGTGCAGGTCTCCAGTCCTG
CCTCCTCTCCTCCACCCGTAAGAACAAGGGAAATC
CCACAGAACCCTCTGCCCCGGGGAGCATTTAAATC
AGCTTAGTCTATCTCCAGGTCGCTACCCCGCCCCA
GCCCAACACCCAGGCCTCAGTCACCCTAGACAGAG
ATTCCCGTACCCAGGCAGGCAAGGGACCCTAACAC
ATCCCAGCCCGCTGGTGGTCACGCGCGCAGCCCGG
ACAGGCCAGCAGCCCCCGCCCCGCGAGGACGCCAC
ACTCGCAGCGCCCGGCCCTCCCCTAGCGGAGCCCG
CCCCGTCTCCCTCCGCCCCGCCTCCCTCCGCTCCG
CTCCGCTCCGCTCCGCCCCGCCCCGGGTCCGCAGC
CCCG
ATGGAAGCCACTAGAAGAAGACAACACTTGGGAGC
GACAGGTGGACCCGGTGCGCAGTTGGGAGCCTCCT
TTCTTCAAGCTAGGCATGGTAGCGTAAGTGCTGAC
GAAGCCGCACGCACTGCACCTTTCCACTTGGATTT
GTGGTTTTATTTCACCCTCCAGAATTGGGTTCTGG
ATTTCGGGCGACCCATCGCAATGCTGGTGTTCCCG
CTTGAGTGGTTCCCCCTTAATAAACCCAGCGTGGG
AGACTATTTTCACATGGCATACAACGTGATAACCC
CTTTCTTGCTCCTTAAACTCATAGAGCGCAGCCCC
AGAACGCTTCCCAGAAGCATAACGTATGTGTCCAT
TATTATCTTCATAATGGGTGCCTCAATACACCTTG
TCGGAGATAGCGTAAATCACCGACTCCTCTTTTCA
GGATACCAACACCACCTGAGTGTTAGGGAAAACCC
GATTATTAAGAACCTCAAACCTGAGACCCTTATTG
ATTCTTTCGAGCTGCTGTACTATTACGACGAATAC
TTGGGTCATTGTATGTGGTATATTCCATTCTTTCT
CATTCTCTTCATGTATTTTTCTGGGTGCTTTACGG
CAAGCAAGGCGGAGAGCCTTATCCCAGGCCCCGCG
CTCCTTCTTGTTGCCCCAAGCGGTCTCTATTATTG
GTATCTGGTAACCGAGGGGCAAATATTTATACTTT
TTATTTTCACCTTCTTTGCCATGCTCGCCTTGGTT
TTGCACCAGAAGAGGAAGAGATTGTTCCTCGATAG
CAACGGACTTTTTCTGTTCTCTTCCTTCGCGCTTA
CCCTTCTCTTGGTAGCCTTGTGGGTCGCCTGGCTG
TGGAATGACCCAGTTTTGCGGAAAAAGTATCCCGG
TGTGATCTACGTGCCTGAACCTTGGGCATTCTACA
CTCTTCATGTGTCCTCTAGACACGATTATAAGGAT
GATGATGACAAATA
The CLN8 protein sequence is:
(SEQ ID NO: 78)
MNPASDGGTSESIFDLDYASWGIRSTLMVAGFVFYLGVFVVCHQLSSSLN
ATYRSLVAREKVFWDLAATRAVFGVQSTAAGLWALLGDPVLHADKARGQQ
NWCWFHITTATGFFCFENVAVHLSNLIFRTFDLFLVIHHLFAFLGFLGCL
VNLQAGHYLAMTTLLLEMSTPFTCVSWMLLKAGWSESLFWKLNQWLMIHM
FHCRMVLTYHMWWVCFWHWDGLVSSLYLPHLTLFLVGLALLTLIINPYWT
HKKTQQLLNPVDWNFAQPEAKSRPEGNGQLLRKKRPDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN8 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
CLN8-DNA (SEQ ID NO: 79)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
TGAAATCGTATGGATCAAAGCTGTCCTCTTGGCCT
GAGCCGGTTGCTGAGTGCGGGCCACAAGATCAGAT
GAGCCAGTTTATCCATCTGGATGGTCCCAGCTAAT
TCAGCAAGTGCAAGGTCTGCAAAATATCTCAAGCA
CTGTTGTTAGGTTTTTCAATAGTGATGTTATCCCC
AGGAGCAATTTAGGGAGGGTCAGAATCTTGTAATC
TCCAGCTGCATGAATTCTAAACCATAATTTCTAAT
CTTGTGGCTAATTTGTTAGTCCTACAAAGGCAGTC
TAGTCTCCAGACAAGAAAAGGATTTGTTTCGGGAA
ACCATAAACTAAGTTTCTTCCAAAGTTAGTTTGGC
CTACACCCAGGAATGAACAAGGACAGTTTGGAGGT
TAAAAGTAGGATGGAGTTGGTTAGGTCAGATCTCT
CACTGTCTCAGTTATAATTTTGCAATGGTGGTTTC
ACTGGTTTTAAGATGGAGTTTATTTTATTTTATTT
TTATTTTTTTGAGACAGAGTTTCATTCTTGTTGCC
CAGGCTAGAGTGCCATGGCGTGATCTCAGCTCACT
GCAACCTCTGCCTCCTGGGTTCAAGCAATTCTGCT
TCAGCCTCCTGAGTAGCTGAGATTACAGGTGCCCA
CCACCACACCCGGCTAATTTTTTTCTCCCAAACTG
CTGGGATTACAGGCTTGAGCCACCGCGCCCGCCAA
GATGGGTTGTTGATTTTAAAACGATGTCACCCTGG
CTCTCCTAGGTTCCTGTTCCCCTAACATCATGAAG
GCTGCTGGCAGTTCTCTGGCCTCCAGGGAGGCCTC
CACACACATTTACCCATGTTCTTAGACAATCCTAG
GGACTCAAGGCTTCAACAAACCTAAATGAGCCAGC
AGAAAAATAAACTTGAACATGAATGTCAACGTTTT
CCCACATGTACTAAAGGGTTATAATAATTTTGAAA
TGTTTATTTCAAAGAGCGTTGGTAATTTAAACGTC
CTATTTAATCCCCAAAACAGTCCTGAGGGGGAGAT
AAGGCAGTTATCTTCATAGTACAGGAAAGGAAAAA
AGCGAGGGTCCAAGGCCGACTATACCCTCAGCTCC
ATTAGCCCCCGAGGCCTCCCTGACAGGCGGGGCGG
ACAATCCCAGTGCAGATGCTCTGTATCGATCGCAT
GCTATCGGTTCTTTCAAGGAACGTGTATTGATCAT
CAATTAAGTGGTGAGTACTCCTCTAGATGTCGATT
CTAAAGAGGGAACAAAACACATTAGACAGAAGAAA
CATAAGTAACTCGAATAACAACCTTAGAGAGAAGA
AACATAAGTAACTCGAATAACAACCTTAGCAAACT
GCGGAAACTCCTACAGACAAAAACTCAGGTGTGGG
CGCAGAAGGGCCGGGGATGCGCTCGGTCAAGACTT
GAAGGTCCGGGGCTTGGGCCCTGTGTCCTCACCGA
GCCCCGGGGAGGCTCCGGCTCCGTCCACACCCGGA
GCGCGACTCAGCCGCGGCCGGGGCTCTTCTGGAGA
ACGGCGCGGTCAGGCTCTGCCGCAGCTTTCAGGTC
CCCTCGGCCCCGTCCGGGTGCAGCGCAACCAGGCT
GCCCGCGGAGCCCCACCGCCCCCATGCCGCCGCCC
GCCATGGTTCAGCCCGGCCCCGCCCCTCCCGCCGG
CCGTGGTTCAGCGCGTCCACCCCGCCGCCCCACAG
CGCCCGCCGCGCCGCGCCCCGCCCCCCGCCGCGCC
CCGCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCC
CGCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCC
GCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCG
CCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCGC
CCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCGCC
CCCCGCCGCGCCCCGCCCCCCGCGCCGCGCCCCGC
CCCCCGCCGCGCCCCTCCCGCGCCCGCCGCCCCGC
CCCTCCCGCGCCCGCCGCCGTCGTAGCGCCTAGGC
GGGGCCTCTCGTAGCGACGCCCCCAGGGGGGCAGA
ACGCGTGCGCACGCGCGTGCGAACGCGCGTGCGCG
GGCGGTGTTTGAGGCCGGC
ATGAATCCCGCGAGTGATGGCGGCACTTCAGAGAG
TATCTTTGACTTGGACTATGCATCATGGGGGATAC
GCTCAACTCTTATGGTTGCAGGGTTCGTATTTTAT
CTGGGGGTTTTTGTTGTCTGTCACCAACTTTCCAG
CAGTCTCAACGCCACTTATAGATCCCTTGTGGCTA
GGGAGAAAGTCTTTTGGGACTTGGCCGCAACCCGA
GCCGTTTTTGGTGTCCAGTCCACGGCGGCTGGACT
GTGGGCCCTCCTTGGTGATCCTGTTCTGCACGCTG
ATAAAGCCAGAGGCCAACAGAACTGGTGTTGGTTC
CATATAACTACGGCGACTGGCTTCTTTTGTTTTGA
AAACGTAGCCGTACACCTGTCCAATTTGATCTTCA
GAACATTCGACCTCTTTCTGGTAATCCACCATCTT
TTCGCCTTTCTCGGCTTTCTTGGATGTCTTGTCAA
TCTCCAAGCCGGTCACTACCTCGCAATGACTACTT
TGTTGCTCGAAATGTCAACCCCATTTACTTGCGTA
TCATGGATGCTGCTGAAAGCGGGATGGAGTGAATC
ACTTTTTTGGAAGTTGAATCAGTGGTTGATGATTC
ATATGTTTCACTGTCGAATGGTACTGACATATCAT
ATGTGGTGGGTCTGTTTCTGGCACTGGGACGGGCT
GGTATCTTCACTTTATCTCCCTCACCTGACCCTTT
TCCTCGTAGGCTTGGCGCTGCTCACACTGATCATT
AATCCTTACTGGACCCACAAGAAAACGCAGCAACT
GCTGAACCCTGTGGATTGGAACTTCGCACAGCCCG
AGGCCAAGTCACGGCCTGAAGGCAACGGTCAACTG
TTGAGGAAGAAGAGACCGGACTATAAGGATGATGA
CGACAAATA
The GM2A protein sequence is:
(SEQ ID NO: 80)
MQSLMQAPLLIALGLLLAAPAQAHLKKPSQLSSFSWDNCDEGKDPAVIRS
LTLEPDPIIVPGNVTLSVMGSTSVPLSSPLKVDLVLEKEVAGLWIKIPCT
DYIGSCTFEHFCDVLDMLIPTGEPCPEPLRTYGLPCHCPFKEGTYSLPKS
EFVVPDLELPSWLTTGNYRIESVLSSSGKRLGCIKIAASLKGIDYKDDDD
K
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GM2A and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
GM2A-DNA (SEQ ID NO: 81)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
CCCAGATACAGAATCTTCTTGGGTCCAAATACCCC
CTAGAGGTTTCCCATTGGCCACTTGGTGCTCACCT
CATGTAAATGAAGTGGTGGCCCGCAATCAGTCTGA
CTGGTTAATCAGAGGCCGAAGTGAAGTTACAAAGG
TCATGCTCCTGTGCAAACATCTGATTGGTTGTGGA
AAGCAACCAATCAGGCTGAAGTGAAGTTACAAAGT
TGCACTTCTATGCAATTTTAACATATAAACTGAAA
TGTAGCATAGAAATCGAAATGTACTTTCAATTTCC
CATCTGCTGCACAGAAAAGGTGGGGGGTTGTAAAG
AGAGTAGCCTCTGGTCCTCTTGTTACTTAGGTGTG
GAAAGTTAGGGTTTTCCTTTCGATTTAGTTCTAGG
AAGTCAGCGTGAAATGGCCTTAGGTTCCCTGCCTG
CAGACTCTATTCTCCTACCTCAGTTGGGCTAGGTG
AAAGGGAAGAGTTGATCAGAATGGGAGGATCATTA
TGTAAAGTATGGAGCTTAGTTAATAATAGTGTACC
AATGTCATGCCCTCAGATTTAAAAAAAATTTTTTA
ATTTTTTATTCTTTTGCCACCTCCTTGTCGCTGGC
AGTGCCCCCCAGTTATGCACAAGCACAAGCTCTGG
GTCTGCAGTCTGAACCCCCGGCCAGGCCACGGGTG
TCTTATCAACAATAGAGGAAACGAACAGAACTTTG
TAGTATTTTTGCAACTTTTCTGTAAACCAAAATAA
AAAGTTTACTTTAAAAAAGATGATCAGGTGAGTTT
TAAATTCTACACATGCATTCATGTACTCAACAGAT
TGTCTATTATGCATCAGGCACTGGGTATAAATGAG
TGCCTGCATCATGATGCCACCCCTTGTGTAGTTTA
CAATCCTGTGGTAAATTGGCGGTATTGGTAACAAC
ATCCCTGTTTTTTCTAAAAGCAAATCTCCAACTAG
TATATTAACCTGACAAAATCTTGGCTGATGGGGTG
TCTAAAAAGAAGTCTTGCTCTATTCCTTCCTAGCT
GTGCGACCTTGGCAGAGCTAACCTCACTGTGTATC
AGTTTCCTCAGTGCTAAAATTGGGGAAGAAAAAAA
AAAAGCATTCCCTTGTGCGTCCTTAGCATGCTTTC
AAGCAGTTACTAAATGTTAGTTTTTATAACGGTTA
TAATTATTAAAAAGATACGGATTCGTGAAGTCAAG
AGATCAAGACCGTCCTGGACAACACGGTGAAACCC
CGTTTCTACTAAAAACACAAAAATTAGCTGGGCGT
GTGGCGCGTGCCTGTAGTCCCAGCTAGTCGAGAGG
CTGAGGCGGAAGAATCGCTTGAACCTGGGAGGCAG
AGGTTGCAGTGAGCCGAGATCGCGCCACTGCACTC
CAGCTCGGGCGACAGAGCGAGAGTCCGTCTCAAAG
CAAAAAAAAAAAAAAAAAAGACACACATATGGGGA
AGCGTAACATGGCAGAGAGTCTGACATTTTTGTCC
GGAAGGACTTGGGGATGAAAACACTGAATCCGCGG
TTTCCCAAAGGTCCTTCCAAAGGTGACGGCCCCGG
CACGAGTTCACAAACCACAGCTCCGCCCCATCCCC
TGCCCGGCCCCGCCCTTCCCAGGAGCTCTGCTCCG
CCCCGCCCCCGACTCCGCTCGGCCCCTCCTCGCGC
CACGCCCCCGCCCCTCCCGCGCGCGCAGCTCCGCC
CCGCCCTCGTGATCCCGCCCCAACCTCGTGCTAAG
CTCCCTTCCGTTCCAGCCGCCTTCAGCCCCGCCGC
GCTCAGTTCCGCCCCTTTCTCTTCCAACTCCGCCT
ACGCCCCAGAGAGGGAAGGCCTTGACACCTACGCT
AGAGAGACAGGCTCCAATGAAAAGAGCGAGGGGGC
GGAGCCGGGAGGAATCGGTCCAATTCTCGGCCGGG
AAGTCTCTGGCCGGGACGGGGCAGGGCGAACCTGC
CAGTGACTGGACTCAGCTTCTTTGCGTAACCAATA
CTGGAAGGCATTTAAAGGCACCTCTGCCGCCACAG
ACCT
ATGCAGTCTCTCATGCAAGCTCCTCTCTTGATCGC
CCTTGGTCTGCTTTTGGCTGCCCCAGCACAAGCTC
ACCTGAAAAAACCTTCCCAACTTAGCTCCTTTTCC
TGGGATAATTGCGATGAAGGAAAGGACCCGGCTGT
AATCCGAAGTTTGACACTCGAACCTGACCCCATCA
TCGTCCCGGGCAATGTCACGCTTTCAGTAATGGGT
AGCACGAGCGTTCCGCTCTCTAGCCCATTGAAAGT
AGACCTCGTGTTGGAAAAAGAAGTAGCCGGGTTGT
GGATAAAAATTCCATGCACGGATTATATTGGCTCA
TGTACCTTTGAACACTTTTGCGATGTTTTGGACAT
GTTGATCCCCACAGGCGAGCCATGTCCAGAGCCCC
TTAGGACGTATGGGCTTCCGTGTCACTGCCCATTC
AAGGAAGGTACATATAGCCTGCCGAAGTCAGAATT
TGTCGTCCCTGATCTCGAATTGCCTAGTTGGCTGA
CAACCGGCAACTATCGAATTGAATCTGTACTTTCT
TCAAGCGGTAAACGGCTCGGCTGTATCAAAATAGC
CGCCTCCCTGAAGGGGATAGACTACAAGGACGACG
ACGATAAATA
The HYAL1 protein sequence is:
(SEQ ID NO: 82)
MAAHLLPICALFLTLLDMAQGFRGPLLPNRPFTTVWNANTQWCLERHGVD
VDVSVFDVVANPGQTFRGPDMTIFYSSQLGTYPYYTPTGEPVFGGLPQNA
SLIAHLARTFQDILAAIPAPDFSGLAVIDWEAWRPRWAFNWDTKDIYRQR
SRALVQAQHPDWPAPQVEAVAQDQFQGAARAWMAGTLQLGRALRPRGLWG
FYGFPDCYNYDFLSPNYTGQCPSGIRAQNDQLGWLWGQSRALYPSIYMPA
VLEGTGKSQMYVQHRVAEAFRVAVAAGDPNLPVLPYVQIFYDTTNHFLPL
DELEHSLGESAAQGAAGVVLWVSWENTRTKESCQAIKEYMDTTLGPFILN
VTSGALLCSQALCSGHGRCVRRTSHPKALLLLNPASFSIQLTPGGGPLSL
RGALSLEDQAQMAVEFKCRCYPGWQAPWCERKSMWDYKDDDDK
The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HYAL1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.
HYAL1-DNA (SEQ ID NO: 83)
GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA
GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA
CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT
GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC
AATAATGACGTATGTTCCCATAGTAACGCCAATAG
GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA
CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA
TCATATGCCAAGTACGCCCCCTATTGACGTCAATG
ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC
ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT
CTACGTATTAGTCATCGCTATTACCATG
GGACTTGCTGGTGACACAGCCTCAGGAAGTCCTGA
GGACATGTGCCCAGGGCGGTTGGGGCACAGCTTGG
TTTTATAGATTTTAGGGAGACATGAGACATTAATC
AATATGTAAGAAGTACATTAGTTCCAGAAAGAAAG
GTGGAGACTGCTCAAATCAAGGCTCCCAGGCTCAA
AGCACTGGGGGCTTCCAGGTCACAGATAGGTGAGA
GACAGATGGTTGCATTCTTTTGAGTTTCTGGTAAG
TCTTTCCAAAGGAGGCAATCAGAATATGCATCTAT
CTCTGTGAGCAAAAGGATGACTTGAATAGAATGGG
AGGCAGATTTGTCCTGAGCAGTTCCCAGCTTGAAG
AGGCCCAAGATACTTTCCTTTCACATTTACCCCAT
TTTCTTTTTCAAAATCTTTTGGAGAAAGCATTTTG
CAAGAAAATGAGTATCTGGTCTCAGGTTTCATCTG
ATCTCTCATTGCTAGATAAGTAGGTCCGGAAAGCT
CATTTTTAGCAGGTTGTAAAGTCTCATGCAGTGTG
AAGAGAAAATAGGGAGAAGGAAGGAAGAGAAAAAA
AAAACAGCAAAAGAACAATCCCAGCCCTGGCGGGG
TGGCTCATGCCTGTAATCCCAACAATTTGGGAGGC
TGAGGCGGGTGGATCACCTGCGGTTGGGAGTTCGA
GAACAGCCTGACCAACATGGAGAAACTCTGTCTCT
ACTGAAAATACAAAAAACTAGCCAGGCATGGTGGC
TCATGCCTGTAATCCCAGCTACTCAGGAGGCTGAG
ACAGGAGAATCACTTGAACCCAGGAGGCGGAGGTT
GCAGCAACCTGACATTGCGCCATTGCACTCCAGCC
TGGGCAACAAGAGTGAAACTCCATCTCAAAAAAAA
AAAAAAAAAAAATCCTGGGAAAATATAGGCCACAT
TACTCTGAAGTCCATACATTGGTAGGCAGGTATGA
AAGTGGCTTATGTATGTACATAAACAGGTTACTGT
TACTTTCTTCTGAAGTGTAAGTTGTCTGACTTTAG
TTGACACGCTTTTAAGAAACCACAGCTAGGGCCGG
GCGCAGTGACTAACGCCTGTAATCCCAGCACTTCG
AAGAGGCCGAGGCGGCCGGATCACAAGGTCAGGGT
TCGAGACCAGCCTGGTCAATATGGTGAAACCCTGT
CTCTACTAAAAATACAAAAATTAGCCAGGCATGGT
AGCAAGCGCCTGTAGTCCCAGCTACTCGGGAGGCT
GAGGCAGGAGAATTGCTTGAACCTGGGAGGCATAA
GTTGCAGTGAGCTGAGATCGCGCCACTGCACTCCA
GCCTGGGTGACAGAGCGAGACTCCATCTCAAAAAA
AAAAAAAAAAGAAACCACAGTGGCCGATTGCAGTG
GCTCCCCCTCCCCCTCCCCCTCCCCTCCCCCTCCC
CCTCCCCCTCTCCCTCCACGGTCTCCCTCTGATGC
CGAGCGGAAGCTGGACTGTACTGCTGCCATCTCGG
CTCACTGCAACCTCCCTGCCTGATTCTCCTGCCTC
AGCCTGCCGAGTGCCTGCGATTGCAGGCACGCGCC
GCCACGCCTGACTGGTTTTCGTATTTTTTGGGTGG
AGACGGGGTTTCGCTGTGTTGGCCGGGCTGGTCTC
CAGCTCCTAACCGTGAGTGATCTGCCAGCCTCGGC
CTCCCGAGGTGCTGGGATTGCAGACGGAGTCTCTC
AATGGTGCCCAGGCTGGAGTGCAGTGGCGTGATCT
CGGCTCGCTACAACATCCACCTCCCAGCAGCCTGC
CTTGGCCTCCCAAAGTGCCGAGATTGCAGCCTCTG
CCCGGCCGCCACCCCGTCTGGGAAGTGAGGAGCGT
CTCTGCCTGGCCGCCCATCGTCTGGGATGTGAGGA
GCCCCTCTGCCTGGCTGCCCAGTCTGGAAAGTGAG
GAGCGTCTCTGCCCAGCCGCCATCCCATCTAGGAA
GTGAGCAGCGCCTCTTCCCGGCCGCCATCCCATCT
AGGAAGTGCGGAGCCTCTCTGCCCGGCCACCCATC
GTCT
ATGGCAGCGCATCTCCTCCCGATATGTGCACTTTT
TCTGACTCTTCTTGATATGGCACAAGGATTTCGGG
GTCCGCTCTTGCCTAATCGACCTTTTACAACAGTA
TGGAATGCTAACACACAGTGGTGCCTTGAAAGGCA
CGGTGTCGACGTTGACGTCTCCGTCTTCGACGTAG
TAGCCAATCCAGGCCAAACCTTCAGGGGGCCAGAT
CATGACTATCTTCTATAGTTCTCAACTGGGGACTA
TCCCTACTACACCCCCACGGGTGAACCTGTATTCG
GCGGGTTGCCACAGAATGCTAGCCTTATCGCGCAC
CTGGCCAGGACGTTTCAAGACATACTCGCCGCCAT
TCCAGCACCCGACTTCTCTGGTCTGGCTGTGATCG
ATTGGGAGGCCTGGCGACCTAGGTGGGCTTTCAAC
TGGGATACCAAGGACATCTATAGGCAGCGGAGCCG
AGCATTGGTGCAAGCCCAGCATCCGGATTGGCCAG
CGCCTCAGGTGGAAGCGGTAGCGCAGGATCAATTC
CAGGGCGCCGCGAGAGCTTGGATGGCCGGGACATT
GCAACTTGGGAGAGCCTTGAGGCCTCGCGGCCTGT
GGGGTTTTTATGGATTCCCAGATTGCTACAACTAT
GATTTTCTCTCTCCAAATTACACAGGCCAATGTCC
AAGCGGCATACGCGCACAGAACGATCAGCTTGGCT
GGCTCTGGGGACAATCTCGAGCCTTGTACCCTAGC
ATCTATATGCCAGCTGTCTTGGAGGGCACCGGAAA
ATCTCAGATGTACGTGCAACATAGGGTTGCAGAGG
CCTTCCGGGTTGCCGTCGCAGCCGGAGATCCGAAT
CTGCCTGTTCTTCCCTATGTACAGATCTTTTATGA
TACCACAAATCACTTTTTGCCGTTGGACGAGCTTG
AACATAGTTTGGGTGAAAGTGCGGCCCAAGGTGCG
GCGGGAGTAGTTCTTTGGGTTTCCTGGGAAAATAC
ACGGACTAAAGAGTCATGTCAGGCCATAAAGGAGT
ACATGGATACCACACTGGGCCCTTTCATTTTGAAT
GTTACGAGTGGCGCGTTGCTTTGTAGTCAGGCACT
GTGCAGCGGACACGGCAGGTGTGTGCGGCGGACGT
CACATCCAAAGGCCCTGCTGCTGCTGAACCCGGCG
TCATTTTCAATTCAACTTACTCCCGGTGGGGGGCC
CCTCTCACTTAGGGGCGCGCTCTCCCTGGAAGACC
AGGCCCAGATGGCAGTAGAGTTTAAGTGCAGATGT
TACCCAGGGTGGCAGGCGCCTTGGTGCGAGCGCAA
ATCCATGTGGGATTACAAAGATGATGATGATAAGT
A
In certain embodiment, any of the GOI described herein are codon optimized for manufacturing, optimal expression in a host cell, such as in a human cell. Further Codon optimization of GOI can be done based on codon optimization table publically available, such as the Codon and Codon Pair Usage Tables (CoCoPUTs) maintained at the George Washington University (GWU). The CoCoPUTs is derived from all available GenBank and RefSeq data source.
In certain embodiment, the GOI's are codon optimized for expression in neuronal tissues or specific cell types in neuronal tissues, such as neurons, depending on the target cell type the GOI's are to be expressed. This can be done using TissueCoCoPUTs, which are human tissue-specific codon and codon pair usage tables derived from human genomic codon usage information and tissue-specific transcriptomic data. The TissueCoCoPUTs maintained by the GWU website represent 52 human tissues. Transcriptomic data are derived from the Genotype Tissue Expression (GTEx) Portal.
3. Delivery Methods In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by intravenous injection or direct intraparenchymal injection or direct intracranial injection. Such delivery means effectively bypass the BBB, and are common means for the administration of gene therapeutics to the brain. In certain embodiments, the neuronal target cells intended to receive gene therapy through intraparenchymal injection are clustered in a focal location, and are this particularly suitable for focal delivery of the viral vector.
In certain embodiments, the viral vector (such as AAV) of the invention is delivered locally or compartmentally, such as direct intraocular injection, or injection in the cochlea.
In certain embodiments, the viral vectors of the invention are delivered to neuronal target cells by intravenous injection.
In certain embodiments, the neuronal target cells intended to receive gene therapy through intravenous injection are globally located in the CNS, or in multiple CNS regions. Such global delivery across the BBB is achieved by using selected AAV serotypes (such as AAV9) that have been shown to deliver genes across the BBB after intravenous injection.
In certain embodiments, the viral vector (such as AAV) of the invention is delivered to achieve widespread delivery for diseases of extensive pathology including glioblastoma multiforme (GBM), lysosomal storage diseases (LSDs), Alzheimer's disease, Parkinson's disease and Canavan's disease. In certain embodiments, the viral vectors are delivered intracerebroventricularly, intrathecally, intranasally, or systemicaly (e.g., intravenous and intra-arterial injections).
The systemic delivery route for gene delivery vehicles is very promising, and has the potential to be a conduit to the entire CNS (every cell in the brain is a maximum distance of 40 μm from an endothelial cell), provided that the issue of BBB blockage and the filtration systems of the spleen and liver are adequately dealt with.
In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by intravascular, intrathecal, and/or cerebrospinal fluid (CSF) administration. Many AAV capsids, such as AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 and rAAVrh.10, have remarkable CNS tropism after vascular (Foust et al., Nat Biotechnol. 27:59-65, 2009; Gray et al., Gene Ther. 20:450-459, 2013; Zhang et al., Mol Ther. 19:1440-1448, 2011; Bevan et al., Mol Ther. 19:1971-1980, 2011; Yang et al., Mol Ther. 22:1299-1309, 2014; Duque et al., Mol Ther. 17:1187-1196, 2009), and CSF administration (Samaranch et al., Hum Gene Ther. 24:526-532, 2013; Gray, supra; Samaranch et al., Hum Gene Ther. 23:382-389, 2012).
In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by direct intracranial injection. A large range of AAV capsids, including pseudotypes rAAV2/1, rAAV2/2, and rAAV2/5, hu.32, hu.37, pi.2, hu.11, rh.8, hu.48R3, bb2, cy5, rh20, rh39, rh43, AAV7, AAV8, and AAV9, have been demonstrated for their CNS gene transfer properties by direct intracranial injection (Burger et al., Mol Ther. 10:302-317, 2004; Cearley et al., Mol Ther. 16:1710-1718, 2008; Cearley and Wolfe, Mol Ther. 13:528-537, 2006; Lawlor et al., Mol Ther. 17:1692-1702, 2009). Vectors based on distinct AAV serotypes or pseudotypes can be chosen for specific applications in the nervous system, depending on their preferential or global tropism within the different regions of the brain and target neuronal tissues.
In certain embodiments, the viral vector is AAV9. The vast majority (>90%) of cells in the CNS transduced by intravenously injected AAV9 using strong promoters like CBA are astrocytes and neurons. The distribution of vector is widespread with transduced cells detected in all areas of the brain from the olfactory bulb to cerebellum.
In certain embodiments, delivery of the viral vectors of the invention across the BBB is further enhanced by a variety of techniques including: intra-nasal administration and/or intracranial NSC transplantation that bypasses the BBB; transiently permeating the BBB using osmotic manipulation; magnetic resonance imaging guided focused ultrasound (MRIgFUS) to selectively open the BBB and allow therapeutics to pass into the parenchyma; convection enhanced delivery (Debinski and Tatter, Curr Opin Mol Ther. 12:647-653, 2010); introduction into a fluid space, e.g., vasculature, brain ventricles or intrathecal space in the spinal cord, such that cells lining the space produce the deficient protein (Chen et al., Nat Med. 15:1215-1218, 2009); injection into regions of the brain that serve as a nexus of interconnections with retrograde transport of vectors, such as the thalamus, e.g., for AAV (McCurdy et al., Sci Transl Med. 6:231ra48, 2014); and/or by taking advantage of the “bystander effect” whereby proteins released from the producer cells can be taken up by the deficient cells (McCurdy; Chen, Supra).
In certain embodiments, the viral vector (such as AAV) of the invention comprises a targeting peptide that bind selectively to the brain endothelial cells or a brain endothelial cell receptor (such as the low-density lipoprotein (LDL) and other related receptors that can be targeted by Apolipoprotein E-derived peptides) to target the viral vector to the brain vasculature.
4. Viral Production Another aspect of the invention provides a method of producing the rAAV vector of the invention, comprising introducing the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.
In certain embodiments, the packaging cell line is a HEK293 cell line, a HeLa cell, or an A549 cell.
In general, the subject rAAV vector can be produced using any of many art-recognized approach. In certain embodiments, the rAAV vector is produced based on the helper-virus-free transient transfection method with all cis and trans components (e.g., vector plasmid and packaging plasmids, along with helper genes isolated from adenovirus) in host cells such as 293 cells. In certain embodiments, the rAAV vector is produced using recombinant herpes simplex virus (rHSV)-based AAV production system, which utilizes rHSV vectors to bring the AAV vector and the Rep and Cap genes into the cells. In certain embodiments, the rAAV vector is produced based on baculovirus system which requires simultaneous infection of insect cells with several baculovirus vectors to deliver the rAAV vector cassette and the Rep and Cap genes. In certain embodiments, the rAAV vector is produced based on the AAV producer cell lines derived from HeLa or A549, which stably harbored AAV Rep/cap genes. The AAV vector cassette can either be stably integrated in the host genome or be introduced by an adenovirus that contained the cassette.
