Abstract: Disclosed herein is an adeno-associated virus (AAV) particle comprising a surface-bound peptide that enhances transduction of cells across the blood-brain barrier (BBB). Also disclosed herein is a modified AAV capsid protein comprising an insertion of a polypeptide that enhances transduction of cells across the BBB, and an AAV particle comprising the modified AAV capsid protein. Specific peptides are provided. Pharmaceutical formulations and method of administering/delivering a nucleic acid to a cell of the brain and/or central nervous system are also disclosed.

Abstract: This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

Abstract: Disclosed herein is an adeno-associated virus (AAV) particle comprising a surface-bound peptide that enhances transduction of cells across the blood-brain barrier (BBB). Also disclosed herein is a modified AAV capsid protein comprising an insertion of a polypeptide that enhances transduction of cells across the BBB, and an AAV particle comprising the modified AAV capsid protein. Specific peptides are provided. Pharmaceutical formulations and method of administering/delivering a nucleic acid to a cell of the brain and/or central nervous system are also disclosed.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: The present invention is in the field of recombinant adeno-associated virus (AAV) vectors. In particular, the invention relates to AAV vectors comprising modified AAV capsid proteins that evade neutralizing antibodies but are still able to transduce hepatocytes. The invention further relates to methods of using the AAV vectors to deliver products to subjects and treat diseases.

Abstract: Disclosed herein are methods and compositions comprising an adeno-associated virus 2.5 (AAV2.5) capsid protein, comprising one or more amino acids substitutions, (e.g., which does not contain a substitution at the position corresponding to amino acid 267 of AAV2.5, or does not contain a serine at the position corresponding to amino acid 267 of AAV2.5) wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

Abstract: Disclosed herein are methods and compositions comprising an adeno-associated virus 2.5 (AAV2.5) capsid protein, comprising one or more amino acids substitutions, (e.g., which does not contain a substitution at the position corresponding to amino acid 267 of AAV2.5, or does not contain a serine at the position corresponding to amino acid 267 of AAV2.5) wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.

Abstract: The present invention provides a method of identifying the strength of one or more unique regulatory elements (URE) having conformational effect on a transcribable reporter sequence.

Abstract: Disclosed herein are methods and compositions for gene therapy, in particular, methods and compositions related to alterations in a capsid protein sequence for altering permissiveness of a promoter within a cell when the promoter and the capsid protein are present within the cell and the capsid protein and the promoter are in the context of a recombinant adeno-associated virus (AAV) particle.

Abstract: The present invention provides methods and compositions comprising an adeno-associated vims (AAV) synthetic inverted terminal repeat (ITR), wherein the ITR may have modified promoter transcriptional function. Additionally provided are vectors and virus particles comprising the same, as well as methods of their use.

Abstract: This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

Abstract: The present invention provides a method of manufacturing circular nucleic acid vectors containing a transgene comprising: (a) contacting a host system with a template, wherein the template comprises at least one flanking cleavage site(s), and (i) at least one phage origin of replication (ORI); (ii) at least one Terminal Repeat (TR), and; (iii) a promoter sequence operatively linked to a transgene; (b) incubating the host system for a time sufficient for replication to occur resulting in circular nucleic acid production; and (c) recovering the circular nucleic acid production, wherein the circular nucleic acid self-anneals.

Abstract: Disclosed herein are methods and compositions comprising an adeno-associated vims 2.5 (AAV2.5) capsid protein, comprising one or more amino acids substitutions, wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.

Abstract: Disclosed herein are methods and compositions comprising an adeno-associated virus 2.5 (AAV2.5) capsid protein, comprising one or more amino acids substitutions, (e.g., which does not contain a substitution at the position corresponding to amino acid 267 of AAV2.5, or does not contain a serine at the position corresponding to amino acid 267 of AAV2.5) wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.

Abstract: This invention relates to viral vectors for delivery of alpha-L-iduronidase to the cornea of a subject and methods of using the same for treatment and prevention of corneal clouding and blindness in a subject due to mucopolysaccharidosis I.

Abstract: This invention relates to modified parvovirus capsid proteins with enhanced transduction efficiency, viral vectors comprising the same, and methods of using the same for delivery of nucleic acids to a cell or a subject.

Abstract: The present invention provides a gene editing system having reduced off target effects comprising (a) a vector comprising a nucleic acid sequence encoding a nuclease, wherein the nucleic acid encoding the nuclease contains within its sequence a regulatory nucleic acid sequence having a first and second set of splice elements defining a first and second intron, wherein the first and second intron flank a sequence encoding a non-naturally occurring exon sequence containing an in-frame stop codon sequence, and wherein the first and second intron are spliced from the mRNA message to produce an mRNA encoding a non-functional nuclease that contains an amino acid sequence encoded by the non-naturally occurring exon; and (b) an oligonucleotide that binds to the regulatory sequence. Further provided are methods of using the gene editing system of this invention to regulate transgene expression.

Abstract: This invention relates to modified parvovirus capsid proteins with enhanced transduction efficiency, viral vectors comprising the same, and methods of using the same for delivery of nucleic acids to a cell or a subject.