AAV mediated aquaporin gene transfer to treat Sjogren's syndrome
View Patent ↗The invention relates to a gene transfer-based method to protect a subject from Sjogren's syndrome. The method comprises administering to the subject an AAV virion comprising an AAV vector that encodes aquaporin-1 (AQP-1) protein. Also provided are AQP-1 proteins and nucleic acid molecules that encode such proteins. Also provided are AAV vectors and AAV virions that encode an AQP-1 protein.
1. A method to treat Sjögren's syndrome-associated xerostomia or xeropthalmia in a subject, comprising administering to the salivary gland or the lachrymal gland of the subject, an AAV vector that encodes an aquaporin-1 (AQP-1) protein.
2. The method of claim 1 , wherein the AQP-1 protein is selected from the group consisting of:
a) an AQP-1 protein comprises at least a portion of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11 and SEQ ID NO:14, wherein the protein is able to form a channel that allows the passage of water; and,
b) an AQP-1 protein comprising an amino acid sequence at least 80% identical to a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11 and SEQ ID NO:14, wherein the protein is able to form a channel that allows the passage of water.
3. The method of claim 1 , wherein the AQP-1 protein comprises the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11 and SEQ ID NO:14.
4. The method of claim 1 , wherein the AAV vector has a nucleic acid sequence at least 90% identical to SEQ ID NO:16 or SEQ ID NO:18.
5. The method of claim 1 , wherein administration of the vector maintains or improves the level of salivary gland function relative to the level of salivary gland function prior to administration of the vector.
6. The method of claim 1 , wherein administration of the vector maintains or improves the level of lachrymal gland function relative to the level of lachrymal gland function prior to administration of the vector.
7. The method of claim 1 , wherein the AAV vector is administered as a virion comprising the AAV vector.
8. The method of claim 7 , wherein the virion is an AAV virion.