Treatment of retinal degeneration using gene therapy

Patent metadata

Field	Value
Publication number	US-10912845-B2
Application number	US-201515121283-A
Country	US
Kind code	B2
Filing date	Feb 24, 2015
Priority date	Feb 25, 2014
Publication date	Feb 9, 2021
Grant date	Feb 9, 2021

Abstract

The present invention relates to an improved method of providing photoreceptor function to a cell, for example for use in the treatment of retinal degeneration. The present invention also relates to compositions and kits, in particular for use in such methods.

First claim

The invention claimed is:

1. A method of providing photoreceptor function to an inner retinal cell, comprising
intraocularly administering a therapeutic composition comprising a nucleic acid vector comprising a nucleic acid sequence encoding human rhodopsin or human photopsin, wherein the nucleic acid is under control of a promoter which directs expression to the inner retinal cells;
expressing the nucleic acid sequence in the inner retinal cell; and
augmenting or restoring photoreceptor function of the retina by providing photoreceptor function to the inner retinal cell, wherein the inner retinal cell is an ON-bipolar cell or an OFF-bipolar cell, and wherein the nucleic acid vector is an adeno-associated viral (AAV) vector.

2. The method according to claim 1 , wherein the composition is an injectable liquid.

3. The method according to claim 1 , wherein the nucleic acid sequence is introduced by intraocular injection.

4. The method according to claim 1 , wherein the promoter is selected from the group consisting of L7, thy-1, recoverin, calbindin, GAD-67, Grm6, and Grm6 enhancer-SV40 fusion.

5. The method according to claim 1 , wherein the method comprises a step of dilating the pupil of an eye to be treated prior to administering the therapeutic composition.

6. The method according to claim 1 , wherein the method further comprises monitoring the vision of a subject who received the therapeutic composition.

7. The method according to claim 1 , wherein a photopsin is selected from the group consisting of Long Wavelength Sensitive (OPN1LW) Opsin, Middle Wavelength Sensitive (OPN1MW) Opsin and Short Wavelength Sensitive (OPN1SW) Opsin.

8. The method according to claim 7 , wherein the nucleic acid sequence comprises i) the rhodopsin (RHO) gene, or a fragment or derivative thereof, or ii) the Cone homo sapiens opsin 1, long wave sensitive OPN1LW gene, or a fragment or derivative thereof; or iii) the Cone homo sapiens opsin 1: medium-wave sensitive OPN1MW, or a fragment or derivative thereof; or iv) the Cone homo sapiens opsin 1, short-wave-sensitive (OPN1SW), or a fragment or derivative thereof.

9. The method according to claim 3 , wherein intra-ocular injection comprises sub-retinal injection or intra-vitreal injection.

10. The method according to claim 4 , wherein the promoter is bipolar cell specific promoter Grm6-SV40 for selective targeting of ON-bipolar cells.

11. The method according to claim 5 , wherein dilating the pupil of an eye to be treated comprises application of a mydriatic agent.

12. The method according to claim 11 , wherein the mydriatic agent is tropicamide and/or phenylephrine.

13. The method according to claim 1 , wherein the AAV vector is a serotype 2 vector, AAV 4YF or AAV 7m8.

14. The method according to claim 1 , further comprising administering an extracellular matrix degradation enzyme prior to, simultaneously with, or subsequent to administering the therapeutic composition.

Assignees

• Univ Manchester

Inventors

• Lucas Robert
• Bishop Paul
• Cehajic-Kapetanovic Jasmina

Classifications

• C07K14/705

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title

• C07K14/723

  G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH receptor · CPC title

• C12N2830/008

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

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title

• C12N9/88

  Lyases (4.) · CPC title