Gene therapy for ocular disorders
Compositions and methods are provided for treating ocular disorders in a subject are provided. In one aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGA3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGB3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding REP-1. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.
1. An adeno-associated virus (AAV) vector comprising an AAV capsid and a nucleic acid sequence comprising AAV inverted terminal repeat (ITR) sequences, a sequence encoding human cyclic nucleotide gated channel alpha 3 (CNGA3), and expression control sequences that direct expression of the CNGA3 in a host cell,
wherein the sequence encoding CNGA3 comprises SEQ ID NO: 9 or SEQ ID NO: 11.
2. The AAV vector of claim 1 , wherein the CNGA3 sequence encodes the protein sequence of SEQ ID NO: 10.
3. The AAV vector of claim 1 , wherein the expression control sequences comprise a chicken β-actin (CBA) promoter with cytomegalovirus (CMV) enhancer elements.
4. The AAV vector of claim 1 , wherein the expression control sequences comprise a rhodopsin kinase promoter.
5. The AAV vector of claim 1 , wherein the ITR sequences are from AAV2.
6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least the AAV vector according to claim 1 .
7. The AAV vector of claim 1 , wherein the capsid is an AAV2, AAV5, AAV8, AAV9, AAV8 bp, or AAV7m8 capsid, or a variant thereof.
8. The AAV vector of claim 1 , further comprising one or more of an intron, a Kozak sequence, a polyA, and post-transcriptional regulatory elements.
9. The AAV vector of claim 1 , wherein the expression control sequence is an ocular cell-specific promoter.