Abstract: The present invention provides for recombinant adeno-associated virus (rAAV) virions comprising a variant capsid polypeptide, wherein the variant capsid polypeptide comprises an alteration to an amino acid corresponding to an adeno-associated virus (AAV) capsid polypeptide amino acid selected from the list consisting of any one or more of V125, V183, N411, Y447, R490, T495, and F536 of SEQ ID NO: 1; and wherein the variant capsid polypeptide comprises an alteration to increase retrograde transport of the rAAV virion by an axon of a neuron. The present invention also provides for recombinant adeno-associated virus (rAAV) variant capsid polypeptides, wherein the variant capsid polypeptide comprises an alteration to an amino acid corresponding to an adeno-associated virus (AAV) capsid polypeptide amino acid selected from the list consisting of any one or more of V125, V183, N411, Y447, R490, T495, and F536 of SEQ ID NO: 1.

Abstract: The present invention provides for heterologous genes of interest coupled to regulatory elements, wherein the regulatory elements comprise nucleotide sequences corresponding to a genomic sequence positioned 3? to a translational start site of an endogenous GPR88 gene.

Abstract: The present invention provides for retro adeno-associated virus (retro-AAV) virions comprising a variant capsid polypeptide, wherein the variant capsid polypeptide comprises one or more alterations that promote retrograde transport of the retro-AAV by a neuron, and a nucleic acid comprising a heterologous gene of interest operatively coupled to a GPR88 and/or a R9P1 regulatory region.

Abstract: Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.

Abstract: Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.