Methods and compositions for treatment of disorders and diseases involving RDH12

Patent metadata

Field	Value
Publication number	US-12419973-B2
Application number	US-202217569896-A
Country	US
Kind code	B2
Filing date	Jan 6, 2022
Priority date	Jul 8, 2016
Publication date	Sep 23, 2025
Grant date	Sep 23, 2025

Abstract

Codon optimized nucleic acid sequences for RDH12 are provided, as well as recombinant viral vectors, such as AAV, expression cassettes, proviral plasmids or other plasmids containing the codon optimized sequence for functional RDH12. Recombinant vectors are provided that express the codon optimized, functional RDH12. Compositions containing these codon optimized sequences are useful in methods for treating, retarding or halting certain blinding diseases resulting from the absence, deficiency or inappropriate expression of RDH12. Other compositions and methods are providing for correcting a non-functional, defective or inadequately expressed native RDH12.

First claim

The invention claimed is:

1. A method of treating Leber Congenital Amaurosis (LCA) due to one or more loss-of function mutations in the gene encoding the retinol dehydrogenase 12 (RDH12) protein in a human subject, the method comprising administering into the subretinal space of at least one eye of the subject an adeno-associated viral (AAV) vector comprising a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 5, wherein the nucleic acid is under expression control of a human rhodopsin kinase 1 (hGRK1) promoter, and wherein the nucleic acid encodes a functional RDH12 protein comprising SEQ ID NO: 2.

2. The method of claim 1 , wherein the human RDH12 DNA is codon optimized for expression in a human cell.

3. The method of claim 1 , wherein a micro injection device is inserted into the subretinal space.

4. The method of claim 1 , comprising administering the AAV vector in an amount of about 10 11 -10 13 viral particles/mL.

5. A method of treating Leber Congenital Amaurosis 13 (LCA13) due to one or more loss-of function mutations in a gene encoding a Retinol Dehydrogenase 12 (RDH12) protein in a human subject, the method comprising administering into a subretinal space of at least one eye of the human subject an adeno-associated viral (AAV) vector comprising a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 5, wherein the nucleic acid is under expression control of a human rhodopsin kinase 1 (hGRK1) promoter encodes a functional RDH12 protein comprising SEQ ID NO: 2.

6. The method of claim 1 , wherein the AAV vector is AAV2/5 or AAV2/8.

7. The method of claim 5 , wherein the AAV vector is AAV2/5 or AAV2/8.

Assignees

• Univ Pennsylvania

Inventors

• Bennett Jean
• Sun Junwei
• Vasireddy Vidyullatha

Classifications

• A61K48/0091

  Purification or manufacturing processes for gene therapy compositions · CPC title

• A61K48/0008

  characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P27/02

  Ophthalmic agents · CPC title