Methods and compositions for treatment of disorders and diseases involving RDH12

Patent metadata

Field	Value
Publication number	US-11197936-B2
Application number	US-201716314179-A
Country	US
Kind code	B2
Filing date	Jul 7, 2017
Priority date	Jul 8, 2016
Publication date	Dec 14, 2021
Grant date	Dec 14, 2021

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 nucleic acid comprising a nucleotide sequence of SEQ ID NO: 5 encoding human RDH12.

2. An expression cassette comprising a nucleotide sequence of SEQ ID NO: 5 encoding human RDH12.

3. The expression cassette of claim 2 , wherein said nucleotide sequence is operatively associated with expression control sequences that can direct expression of the nucleotide sequence in a host cell.

4. The expression cassette of claim 2 , which is a recombinant adeno-associated virus (AAV) expression cassette further comprising a 5′ AAV inverted terminal repeat (ITR) and a 3′ AAV ITR, and expression control sequences that can direct expression of the nucleotide sequence in a host cell.

5. The rAAV expression cassette of claim 4 , wherein the expression control sequences comprise a rhodopsin kinase promoter.

6. A vector or plasmid comprising the expression cassette of claim 2 .

7. A vector or plasmid comprising the expression cassette of claim 4 .

8. A recombinant adeno-associated virus (AAV) comprising an AAV capsid protein and a nucleotide sequence comprising a sequence set forth in SEQ ID NO: 5 encoding human RDH12 under the control of regulatory sequences which can express the human RDH12 in the photoreceptor cells of a subject.

9. The rAAV according to claim 8 , wherein the rAAV comprises an AAV8 capsid, or variant thereof, an AAV7 capsid, or variant thereof, an AAV5 capsid, or variant thereof, or an AAV2 capsid, or variant thereof.

10. The rAAV according to claim 8 , wherein the rAAV is a self-complementary AAV.

11. A host cell comprising the expression cassette of claim 2 .

12. A composition comprising a nucleic acid molecule comprising a nucleotide sequence set forth in SEQ ID NO: 5 encoding human RDH12 under the control of regulatory sequences which can direct expression thereof in ocular cells; and a carrier or excipient suitable for delivery to the ocular cells of a subject.

13. The composition of claim 12 , further comprising a recombinant virus comprising an AAV capsid protein and said nucleotide sequence.

14. The nucleic acid of claim 1 , wherein the nucleotide sequence comprises nucleotides 1 to 949 of SEQ ID NO: 5.

15. The expression cassette according to claim 2 , wherein the nucleotide sequence comprises nucleotides 1 to 949 of SEQ ID NO: 5.

16. The rAAV according to claim 8 , wherein the nucleotide sequence comprises nucleotides 1 to 949 of SEQ ID NO: 5.

17. A rAAV comprising an AAV8 capsid and an expression cassette comprising:
a) a 5′ AAV ITR;
b) a rhodopsin kinase promoter;
c) the nucleotide sequence set forth in SEQ ID NO: 5; and
d) a 3′ AAV ITR.

Assignees

• Univ Pennsylvania

Inventors

• Bennett Jean
• Sun Junwei
• Vasireddy Vidyullatha

Classifications

• A61K48/00 Primary

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

• C12Q1/68

  involving nucleic acids · CPC title

• C12N2800/22

  Vectors comprising a coding region that has been codon optimised for expression in a respective host · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title

• C12N15/67

  General methods for enhancing the expression · CPC title