Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Abstract: Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5? inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3? ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.

Abstract: A recombinant vector having an expression cassette comprising a modified human low density lipoprotein receptor (hLDLR) gene is provided, wherein said hLDLR gene encodes a modified hLDLR comprising (a) one or more of the following amino acid substitutions: L318H, N295D, H306D, V307D, N309A, D310N, L318H, and/or L318D; or (b) an amino acid substitution of any of (a) in combination with one or more of the following amino acid substitutions: K796, K809R and/or C818A. Also provided are pharmaceutical compositions containing this vector and uses therefor in lowering cholesterol and/or treating familial hypercholesterolemia.

Abstract: Provided herein are rAAV and other vectors and compositions useful for treating a patient having CMT2 comprising: (a) a recombinant nucleic acid sequence encoding an engineered human mitofusin 2 coding sequence operably linked to regulatory sequences which direct expression thereof in a human target cell. Also provided are rAAV and other vectors and compositions useful for treating a patient having CMT2 comprising: (b) a nucleic acid sequence encoding at least one miRNA specific for an endogenous human mitofusin 2 sequence in a human CMT2A subject, wherein the miRNA coding sequence is operably linked to regulatory sequences which direct expression thereof in the subject. Further provided are compositions containing both the engineered hMfn2 coding sequence and the at least one miRNA coding sequence, wherein the engineered human mitofusin 2 coding sequence has a sequence which differs from endogenous human mitofusin 2 in the CMT2A patient in the target site of the encoded miRNA.

Abstract: Provided herein are nucleic acid molecules, vectors, and recombinant AAV comprising an inducible gene expression system. The system includes a transgene encoding a gene product operably linked to expression control sequences comprising a promoter; an activation domain comprising a canine or feline transactivation domain and a FKBP12-rapamycin binding (FRB) domain of canine or feline FKBP12-rapamycin-associated protein (FRAP); a DNA binding domain comprising a zinc finger homeodomain (ZFHD) and one, two or three FK506 binding protein domain (FKBP) subunit genes; and at least 8 copies of the binding site for ZFHD (8XZFHD) followed by a minimal IL2 promoter. The presence of an effective amount of a rapamycin or a rapalog induces expression of the transgene in a host cell.

Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Abstract: A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient.

Abstract: Viral vectors comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis and/or cirrhosis in OTCD patients by administering hOTC.

Abstract: Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5? inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional human N-acetyl-alpha-glucosaminidase (hNAGLU), a regulatory sequence which direct expression of hNAGLU in a target cell, and an AAV 3? ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIB.

Abstract: Provided herein are compositions useful for co-administering with a gene therapy vector to a patient having pre-existing neutralizing antibodies to the viral source of the gene therapy vector capsid. The compositions comprise an FcRn ligand which inhibits specific binding between FcRn and IgG.

Abstract: A pharmaceutical composition formulated for delivery of a recombinant adeno-associated virus (rAAV) vector comprising an AAV capsid and a vector genome having human galactosylceramidase (GALC) coding sequence is provided. Also provided are 5 methods and uses of a pharmaceutical composition comprising a rAAV for the treatment of Krabbe disease.

Abstract: A recombinant adeno-associated virus (rAAV) comprising an AAV capsid and a vector genome comprising a frataxin gene is provided. Also provided is a composition containing an effective amount of rAAV to ameliorate symptoms of Freidreich’s ataxia, including, e.g., reduction in progression towards neurocognitive decline and/or cardiomyopathy.

Abstract: A therapeutic regimen useful for treatment of GM1 gangliosidosis comprising administration of a recombinant adeno-associated virus (rAAV) vector having an AAV capsid and a vector genome comprising a sequence encoding human ?-galactosidase is provided. Also provided are compositions containing a rAAV vector and methods of treating GM1 gangliosidosis in patient comprising administration of a rAAV vector.

Abstract: Regimens useful in reducing the frequency of apheresis in a human patient having familial hypercholesterolemia are described. The method involves administering to the human subject via a peripheral vein by infusion of a suspension of replication deficient recombinant adeno-associated virus (rAAV).

Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Abstract: A gene editing nuclease expression cassette is provided which comprises a nucleic acid sequence comprising a meganuclease coding sequence which is operably linked to regulatory sequences which direct expression of the meganuclease following delivery to a host cell, wherein the regulatory sequences comprise a weak promoter. A vector is provided comprising the gene editing nuclease expression cassette. Also provided are compositions containing same and methods of use.

Abstract: A fishing hook includes a base, and a coating, the coating covering the base and providing corrosion resistance to the base.

Abstract: Provided herein is a method for reducing the progression of abnormal muscle pathology and/or reversing abnormal muscle pathology in a patient, wherein the patient has been diagnosed with Pompe disease or is suspected of having Pompe disease. The method comprising administering to the patient a recombinant AAV (rAAV) having an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises: (a) a 5? inverted terminal repeat (ITR); (b) a promoter; (c) a nucleotide sequence encoding a chimeric fusion protein comprising a signal peptide and a vIGF2 peptide fused to a human acid-a-glucosidase (hGAA), (d) a poly A; and (e) a 3? ITR. Also provided are pharmaceutical composition comprising an rAAV described herein for use in treating a patient having or suspected of having Pompe disease.

Abstract: A composition comprising an expression cassette having a nucleic acid sequence encoding one or more elements of a gene editing system that targets UBE3A-ATS on a paternal allele in a neuron of a patient having Angelman syndrome is provided. Also provided is a method for treating one or more symptoms of Angelman syndrome (AS) in a patient having deficient UBE3A expression in neurons, wherein the method comprises delivering a nucleic acid sequence that encodes one or more elements of a gene editing system that targets UBE3A-ATS to modify the UBE3A-ATS coding sequence and provide for expression of paternal UBE3A.

Abstract: A gene editing nuclease expression cassette is provided which comprises a nucleic acid sequence comprising a nuclease coding sequence which is operably linked to regulatory sequences which direct expression of the nuclease following delivery to a host cell, wherein the regulatory sequences comprise a weak promoter. A vector is provided comprising the gene editing nuclease expression cassette. Also provided are compositions containing same and methods of use.