Mutant mammalian RPE65 proteins and portions thereof, and nucleic acids encoding the mutants, for use in treating a condition related to retinal degeneration in a subject, the mutant mammalian RPE65 proteins or portions thereof having isomerohydrolase activity. A gene therapy method of treating a condition related to retinal degeneration in a mammalian subject in need of such treatment, comprising administering to the subject a therapeutically-effective amount of a vector comprising a nucleic acid encoding a mutant mammalian RPE65 protein or a portion thereof. A method of treating a condition related to retinal degeneration in a subject in need of such treatment, comprising administering to the subject a therapeutically-effective amount of at least one of a mutant mammalian RPE65 protein or a portion thereof.

RNA molecules comprising a guide sequence portion having 17-25 contiguous nucleotides in the sequence set forth in any one of SEQ ID NOs: 1-49516 and compositions, methods, and uses thereof.

Methods for assaying function and/or activity and/or potency of isomerohydrolase proteins are provided.

The present disclosure relates to a pharmaceutical composition for the treatment of Leber congenital amaurosis, and a method for treating Leber congenital amaurosis using the pharmaceutical composition.

The invention describes a method for obtaining purified recombinant Adeno-Associated Virus particles (rAAV), comprising the steps of: a) performing a depth filtration of a starting material previously obtained from cells producing rAAV particles, the said starting material being selected in a group comprising a cell lysate and a culture supernatant, whereby a rAAV-containing clarified composition is provided; b) submitting the rAAV-containing clarified composition to an affinity purification step, whereby a first rAAV enriched composition is provided; c) submitting the first rAAV enriched composition at least once to: c1) a step of anion-exchange chromatography on a chromatographic support wherein elution is performed by using a salt gradient, preferably a linear salt gradient, and wherein the rAAV-containing fraction is collected, whereby a second rAAV enriched composition is provided; or c2) a step of density gradient centrifugation, wherein the rAAV-containing fraction is collected, whereby a second rAAV enriched composition is provided; d) submitting the second rAAV enriched composition to a step of tangential flow filtration, whereby purified recombinant Adeno-Associated Virus particles (rAAV) are provided.

The present invention relates to a composition comprising a fusion protein of a cell-penetrating peptide and Retinal Pigment Epithelium-specific 65 kDa (RPE65) as an effective ingredient. With RPE65 increased in cell penetrability, the composition can be advantageously used for treatment of Leber's congenital amaurosis.

The invention describes a method for obtaining purified recombinant Adeno-Associated Virus particles (rAAV), comprising the steps of: a) performing a depth filtration of a starting material previously obtained from cells producing rAAV particles, the said starting material being selected in a group comprising a cell lysate and a culture supernatant, whereby a rAAV-containing clarified composition is provided; b) submitting the rAAV-containing clarified composition to an affinity purification step, whereby a first rAAV enriched composition is provided; c) submitting the first rAAV enriched composition at least once to: c1) a step of anion-exchange chromatography on a chromatographic support wherein elution is performed by using a salt gradient, preferably a linear salt gradient, and wherein the rAAV-containing fraction is collected, whereby a second rAAV enriched composition is provided; or c2) a step of density gradient centrifugation, wherein the rAAV-containing fraction is collected, whereby a second rAAV enriched composition is provided; d) submitting the second rAAV enriched composition to a step of tangential flow filtration, whereby purified recombinant Adeno-Associated Virus particles (rAAV) are provided.

Disclosed is a compound having the Formula (I): X-[NHCHR.sup.1C(O)NHCHR.sup.2C(O)].sub.xY (I) or a pharmaceutically acceptable salt or tautomer thereof, wherein R.sup.1 is H or the side chain of a neutral amino acid; R.sup.2 is the side chain of a basic amino acid R.sup.3; x is inclusive; X is H or a residue of a therapeutic agent; Y is OH, or a residue of a therapeutic agent; R.sup.3 is: [Formula should be inserted here]; R.sup.5 is a residue of a therapeutic agent; and provided that when R.sup.2 is R.sup.3, X is H and Y is OH. Also disclosed is a method of treating an ocular disorder, comprising: (a) intravitreal administration to an eye of a subject in need thereof with an effective amount of a therapeutic nanoparticle composition, the therapeutic nanoparticle composition comprising (i) at least one population of nanostructures and (ii) at least one peptide attached to the at least one population of nanostructures. The nanostructures may be exposed to light in the eye thereby electrostimulating the eye and treating the ocular disorder. Also disclosed is a method of treating an ocular disorder, comprising contacting the eye of a subject in need thereof with an effective amount of a therapeutic nanoparticle composition, the therapeutic nanoparticle composition comprising (i) at least one population of nanostructures, (ii) a peptide attached to the at least at least one population of nanostructures, (iii) a therapeutic agent useful for the treatment of the ocular disorder attached to the at least one population of nanostructures or to the peptide; and (iv) optionally, a linkage between the at least one population of nanostructures or the peptide and the therapeutic agent.

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Methods for preparing highly purified AAV vector formulations are provided. The highly pure AAV formulations described herein are superior for clinical use.

The present invention relates to a composition for gene manipulation for treating or improving a retinal dysfunction disease or a method using the same. More particularly, the present invention relates to a composition for gene manipulation including a guide nucleic acid capable of targeting a retinal function-forming gene and a method of treating or improving a disease caused by retinal dysfunction by artificially manipulating and/or correcting a retinal function-forming gene using the same.