Enhanced AAV-mediated gene transfer for retinal therapies

Patent metadata

Field	Value
Publication number	US-9567376-B2
Application number	US-201414766172-A
Country	US
Kind code	B2
Filing date	Feb 7, 2014
Priority date	Feb 8, 2013
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

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.

First claim

What is claimed is:

1. An adeno-associated virus (AAV) having a recombinant AAV capsid protein comprising SEQ ID NO: 1 or SEQ ID NO: 2.

2. An adeno-associated virus (AAV) having a recombinant AAV capsid comprising a mutation in aa 587-595 of the AAV8 capsid protein sequence as compared to the AAV8 wild type capsid sequence or a mutation in a corresponding region of another AAV capsid protein as compared to the corresponding wild type capsid sequence, further comprising a minigene comprising AAV inverted terminal repeats and a heterologous nucleic acid sequence operably linked to regulatory sequences which direct expression of a product encoded by the heterologous nucleic acid sequence in a target cell, wherein the AAV capsid comprises the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

3. The AAV according to claim 2 , wherein the product encoded by the heterologous nucleic acid sequence is an opsin selected from rhodopsin, photopsin, L/M wavelength opsin (red/green)-opsin, short wavelength (S) opsin (blue), channelrhodopsin and halorhodopsin; NYX, GRM6, TRPM1L or GPR179.

4. A composition comprising an AAV according to claim 2 and a physiologically compatible carrier.

5. The AAV according to claim 2 , wherein the AAV is a self-complementary AAV.

6. The AAV according to claim 2 , wherein the target cell is selected from a photoreceptor, RPE cell, Mueller cell, bipolar cell, ganglion cell, horizontal cell or amacrine cell.

Assignees

• Univ Pennsylvania

Inventors

• Cronin Therese
• Bennett Jean
• Vandenberghe Luk E

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• C12N2750/14122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C07K14/005 Primary

  from viruses · CPC title

• C12N2830/008

  cell type or tissue specific enhancer/promoter combination · CPC title