Abstract: Provided herein are methods and compositions for treating an eye disorder, for example cone-rod dystrophy type 6 (CORD6). In certain aspects, a therapeutically effective amount of a composition comprising nucleic acids is administered to a subject to treat an autosomal dominant disorder or condition, such as a condition associated with a dominant mutation in a guanylate cyclase 2D (GUCY2D) gene, such as knocking out a dominant mutant form of the gene in the subject. Further provided herein are recombinant AAV particles that comprise one or more recombinant AAV genomes comprising nucleic acids that encode a guide RNA that targets a GUCY2D gene and/or an RNA-guided endonuclease.

Abstract: Adeno associated viral (AAV) particles are emerging as a useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (for example, variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.

Abstract: Disclosed herein are compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties.

Abstract: The present disclosure provides for improved recombinant AAV therapies for the treatment of X-linked retinoschisis (XLRS). These therapies are designed for administration to subjects, such as human subjects, including humans diagnosed with or suffering from XLRS.

Abstract: The present disclosure provides AAV8 vectors and variants thereof that express nucleic acids sharing identity to a codon optimized NAGLU (coNAGLU) that improves transduction and distribution in brain cells and will improve disease outcomes in the Mucopolysaccharidoses IIIB (MPS IIIB) mouse model. The present disclosure also provides methods of treatment of a subject, and methods of transducing one or more brain cells, by administering these vectors, as well as uses of these vectors in the manufacture of medicaments for treatment. The present disclosure also provides compositions and host cells comprising rAAV vectors and rAAV particles that express a coNAGLU heterologous nucleic acid and confer enhanced transduction efficiency in human cells, such as brain cells (e.g., neurons). These compositions may be administered to a subject in need thereof.

Abstract: Disclosed are compositions and methods for treating diseases of the mammalian eye, and in particular, complications of the retina associated with Usher syndrome IB (USH1B). Further disclosed are compositions and methods for treating diseases of the mammalian inner ear, and in particular, complications of ear hair cells associated with Usher syndrome IB (USH1B). The disclosure provides improved AAV-based, dual vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. Described herein are modified hybrid dual vector systems that shift the coding sequence for the MY07A tail domain from the front-half vector to the back-half vector by altering the split point (e.g., from between exons 23 and 24, to between exons 21 and 22), in order to eliminate the production of truncated MY07A protein.

Abstract: Adeno associated viral (AAV) particles are emerging as a useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (e.g., variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.

Abstract: Disclosed are viral vector compositions comprising polynucleotide sequences that express one or more biologically-active mammalian guanylate cyclase proteins. Also disclosed are methods for their use in preventing, treating, and/or ameliorating at least one or more symptoms of a disease, disorder, abnormal condition, or dysfunction resulting at least in part from a guanylate cyclase deficiency in vivo. In particular embodiments, the use of recombinant adeno-associated viral (rAAV) vectors to treat or ameliorate symptoms of Leber's congenital amaurosis, as well as other conditions caused by an absence or reduction in the expression of a functional retinal-specific guanylate cyclase 1 (retGC1).

Abstract: Adeno associated viral (AAV) particles are emerging as a useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (e.g., variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.

Abstract: Disclosed are materials and methods for treating diseases of the mammalian eye, and in particular, Usher syndrome 1B (USH1B). The invention provides AAV-based, dual-vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. In one embodiment, vector systems are provided that include i) a first AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a suitable promoter followed by a partial coding sequence that encodes an N-terminal portion of a full-length polypeptide; and ii) a second AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a partial coding sequence that encodes a C-terminal portion of a full-length polypeptide, optionally followed by a polyadenylation (pA) signal sequence.

Abstract: The disclosure provides rAAV particles comprising a new capsid variant, AAV44.9(E531D). The disclosure also provides rAAV particles comprising AAV44.9(E531D) for treatment of the eye, including treatment of retinal disorders. In particular embodiments, the disclosure provides rAAV particles comprising an AAV44.9(E531D) capsid that exhibits enhanced lateral spread after subretinal injection to a fovea of the subject, wherein detachment of the fovea is minimized. The disclosure further provides rAAV particles comprising an AAV44.9(E531D) capsid and a polynucleotide encoding a heterologous nucleic acid sequence. Methods of treatment comprising administering rAAV particles to a mammal in need thereof, and methods of transducing photoreceptor and RPE cells with rAAV particles, are also provided.

Abstract: Disclosed herein are compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties.

Abstract: Disclosed herein are compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties.

Abstract: Disclosed are materials and methods for treating diseases of the mammalian eye, and in particular, Usher syndrome 1B (USH1B). The invention provides AAV-based, dual-vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. In one embodiment, vector systems are provided that include i) a first AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a suitable promoter followed by a partial coding sequence that encodes an N-terminal portion of a full-length polypeptide: and ii) a second AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a partial coding sequence that encodes a C-terminal portion of a full-length polypeptide, optionally followed by a polyadenylation (pA) signal sequence.

Abstract: Adeno associated viral (AAV) particles are emerging as a useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (e.g., variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.

Abstract: Disclosed herein are compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties.

Abstract: Provided herein are methods and compositions for treating an eye disorder, for example CORD6. Aspects of the disclosure relate to knocking out an autosomal dominant mutant GUCY2D gene.

Abstract: The present application provides methods of producing sortable sub-populations of retinal cells. Methods can be used in vivo. Methods can be used to produce sortable sub- populations of cells in non-human primate retina. Methods can be used in conjunction with vivo testing of gene therapy agents and ex-vivo cell sorting and analysis to determine the specificity and/or effectiveness of transgene transduction, transcription, expression, and/or function of the transgene product.

Abstract: Adeno associated viral (AAV) particles are emerging as useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (e.g., variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.

Abstract: Provided herein are methods and compositions for expressing Otoferlin, e.g., utilizing adeno-associated viral (AAV) particles. Such methods and compositions may be useful for treatment of diseases such as Deafness, Autosomal Recessive 9 (DFNB9).