Abstract: Compositions are provided that comprise a recombinant vector carrying a nucleic acid sequence encoding a fragment of CEP290 lacking all or part of its N-terminal and C-terminal inhibitory regions, under the control of regulatory sequences which express the product of said gene in a selected cell of a mammalian subject, and a pharmaceutically acceptable carrier. These and other compositions are disclosed with are useful in methods for treating a mammalian subject having a disease associated with a CEP290 mutation, such as Lebers Congenital Amaurosis.

Abstract: The present invention relates to the synergistic combination of the short and long Rod-Derived Cone Viability Factors and to methods for treating retinal degenerative diseases.

Abstract: Proviral plasmids contain a modular gene expression cassette with one or a combination of (i) a wildtype 5? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of the ITR; (ii) a promoter flanked by unique restriction sites that permit ready removal or replacement of the entire promoter sequence; (iii) a polylinker sequence that permits insertion of a gene coding sequence without modification thereof, wherein the gene is operatively linked to, and under the regulatory control of, the aforementioned promoter; (iv) a bovine growth hormone polyadenylation sequence flanked by unique restriction sites that permit ready removal or replacement of the polyA sequence; and (v) a wildtype 3? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of the 3? ITR.

Abstract: The present invention provides a reading test to measure vision loss. In one embodiment, the vision loss is due to disease progression. The tests are useful in evaluating the effects of intervention in vision deterioration. The tests are non-invasive, simple, quick, sensitive, reproducible, and easy to administer. The tests measure the subject's reading speed and accuracy under defined conditions of illumination and contrast. The results of these tests may be used to determine if treatment of a disease should be initiated, terminated, altered, or remain unchanged.

Abstract: A test of visual function and/or functional vision may be performed at varying luminance levels. A first course may be selected for a subject. A given course may comprise a layout having a beginning point, at least one turn, at least one obstacle, and an ending point. The first course may be illuminated with a first luminance level based on an estimated lower light sensitivity cutoff. The subject may be prompted to perform a first run of the test. The test may comprise, from the beginning point to the ending point, navigating the layout of the first course by walking around the at least one turn and avoiding the at least one obstacle. A determination may be made as to whether the subject successfully completed the first course based on one or both of speed or accuracy.

Abstract: A self-regulating gene expression construct comprises a single promoter in operative association with a repressor sequence (e.g., bacterial repressor lacI or gaiR), operator sequence(s) responsive to the expressed repressor protein, and a transgene. A dual-regulating construct comprises a single promoter controlling expression of a bacterial repressor sequence and a transgene, and which, in the presence of a first inducer molecule, transcribes the transgene and repressor; and a ribozyme in association with an aptamer sequence, the aptamer sequence capable of interacting with a second inducer molecule to terminate mRNA degradation by the ribozyme. Also provided are recombinant vectors or viruses containing the self-regulating or dual self-regulating constructs and cells containing the vectors. Such compositions are useful in methods of treating a diseases using gene therapy.

Abstract: Described herein are capsid proteins and adeno-associated viruses capable of targeting various types of ocular cells including bipolar and horizontal cells. Also described herein are methods of treating various ocular disorders in a subject in need thereof by administering to the subject an effective concentration of a composition comprising the recombinant adeno-associated virus (AAV) of the invention.

Abstract: Described herein are capsid proteins and adeno-associated viruses capable of targeting various types of ocular cells including bipolar and horizontal cells. Also described herein are methods of treating various ocular disorders in a subject in need thereof by administering to the subject an effective concentration of a composition comprising the recombinant adeno-associated virus (AAV) of the invention.

Abstract: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.

Abstract: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.

Abstract: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.

Abstract: Compositions are provided that comprise a recombinant vector carrying a nucleic acid sequence encoding a fragment of CEP290 lacking all or part of its N-terminal and C-terminal inhibitory regions, under the control of regulatory sequences which express the product of said gene in a selected cell of a mammalian subject, and a pharmaceutically acceptable carrier. These and other compositions are disclosed with are useful in methods for treating a mammalian subject having a disease associated with a CEP290 mutation, such as Lebers Congenital Amaurosis.

Abstract: Proviral plasmids contain a modular gene expression cassette with one or a combination of (i) a wildtype 5? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of said ITR; (ii) a promoter flanked by unique restriction sites that permit ready removal or replacement of the entire promoter sequence; (iii) a polylinker sequence that permits insertion of a gene coding sequence without modification thereof, wherein the gene is operatively linked to, and under the regulatory control of, the aforementioned promoter; (iv) a bovine growth hormone polyadenylation sequence flanked by unique restriction sites that permit ready removal or replacement of said polyA sequence; and (v) a wildtype 3? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of the 3? ITR. These plasmids enable rapid manipulation of the components of the cassette, e.g.

Abstract: Proviral plasmids contain a modular gene expression cassette with one or a combination of (i) a wildtype 5? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of said ITR; (ii) a promoter flanked by unique restriction sites that permit ready removal or replacement of the entire promoter sequence; (iii) a polylinker sequence that permits insertion of a gene coding sequence without modification thereof, wherein the gene is operatively linked to, and under the regulatory control of, the aforementioned promoter; (iv) a bovine growth hormone polyadenylation sequence flanked by unique restriction sites that permit ready removal or replacement of said polyA sequence; and (v) a wildtype 3? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of the 3? ITR. These plasmids enable rapid manipulation of the components of the cassette, e.g.

Abstract: A method for enhancing repair of damaged mammalian tubular epithelial cells involves delivering to the tubular epithelial cells of a subject in need thereof a composition comprising an adeno-associated virus (AAV) comprising an AAV capsid having an amino acid sequence of a selected AAV serotype, and a minigene having AAV inverted terminal repeats and a Sec10 gene operatively linked to regulatory sequences that direct expression of Sec10 in the epithelial cells. In one embodiment, delivery is accomplished by retrograde intrauretal injection. In an embodiment the AAV vector includes a capsid of AAV serotype 2/8. Therapeutic compositions containing such AAV are provided.

Abstract: Described herein are capsid proteins and adeno-associated viruses capable of targeting various types of ocular cells including bipolar and horizontal cells. Also described herein are methods of treating various ocular disorders in a subject in need thereof by administering to the subject an effective concentration of a composition comprising the recombinant adeno-associated virus (AAV) of the invention.

Abstract: A test of visual function and/or functional vision may be performed at varying luminance levels. A first course may be selected for a subject. A given course may comprise a layout having a beginning point, at least one turn, at least one obstacle, and an ending point. The first course may be illuminated with a first luminance level based on an estimated lower light sensitivity cutoff. The subject may be prompted to perform a first run of the test. The test may comprise, from the beginning point to the ending point, navigating the layout of the first course by walking around the at least one turn and avoiding the at least one obstacle. A determination may be made as to whether the subject successfully completed the first course based on one or both of speed or accuracy.

Abstract: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.

Abstract: Proviral plasmids contain a modular gene expression cassette with one or a combination of (i) a wildtype 5? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of said ITR; (ii) a promoter flanked by unique restriction sites that permit ready removal or replacement of the entire promoter sequence; (iii) a polylinker sequence that permits insertion of a gene coding sequence without modification thereof, wherein the gene is operatively linked to, and under the regulatory control of, the aforementioned promoter; (iv) a bovine growth hormone polyadenylation sequence flanked by unique restriction sites that permit ready removal or replacement of said polyA sequence; and (v) a wildtype 3? AAV2 ITR sequence flanked by unique restriction sites that permit ready removal or replacement of the 3? ITR. These plasmids enable rapid manipulation of the components of the cassette, e.g.

Abstract: A method for enhancing repair of damaged mammalian tubular epithelial cells involves delivering to the tubular epithelial cells of a subject in need thereof a composition comprising an adeno-associated virus (AAV) comprising an AAV capsid having an amino acid sequence of a selected AAV serotype, and a minigene having AAV inverted terminal repeats and a Sec10 gene operatively linked to regulatory sequences that direct expression of Sec10 in the epithelial cells. In one embodiment, delivery is accomplished by retrograde intrauretal injection. In an embodiment the AAV vector includes a capsid of AAV serotype 2/8. Therapeutic compositions containing such AAV are provided.