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AssigneesGenzyme Corporation, Boehringer Ingelheim Animal Health USA Inc.
InventorsMonica Dias Figueiredo, Sirkka R M Kyostio-Moore, Patricia Berthelette
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The present disclosure relates to recombinant viral vectors, to pharmaceutical compositions comprising such recombinant vectors, and to methods for prevention and treatment of osteoarthritis in mammals. In particular, this disclosure provides adeno-associated virus (AAV) vectors capable of expressing, in a host, osteoprotective/chondroprotective bioactive proteins, including hyaluronan synthase 2 (HAS2) and lubricin (PRG4). Methods of production of these AAV are provided, as are methods of treatment of osteoarthritis in mammalian joints, by the long-term gene expression of osteoprotective/chondroprotective proteins, including HAS2 and PRG4, in both synovial and chondrocyte cells.
A recombinant adeno-associated virus (rAAV) comprising a rAAV vector, wherein the rAAV vector comprises a DNA genome comprising a nucleic acid sequence encoding a canine hyaluronan synthase 2 (HAS2) polypeptide operably linked to a promoter, wherein the rAAV comprises an AAV5 capsid, wherein the nucleic acid sequence encodes a HAS2 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.
A method of treating a mammalian subject suffering from osteoarthritis (OA), comprising intra-articularly administering to said mammalian subject a therapeutically effective amount of a recombinant adeno-associated virus (rAAV) comprising an rAAV vector, wherein the rAAV vector comprises a DNA genome comprising a nucleic acid encoding a canine hyaluronan synthase 2 (HAS2) polypeptide operably linked to a promoter, wherein the polypeptide is expressed in vivo in the mammalian subject in an amount effective to alleviate the symptoms of OA, wherein the rAAV comprises an AAV5 capsid, and wherein the nucleic acid encodes a HAS2 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.
A method of increasing the production of hyaluronic acid in chondrocytes and/or synoviocytes of a canine, comprising the steps of administering a rAAV to the canine, wherein the rAAV comprises a rAAV vector, wherein the rAAV vector comprises a DNA genome comprising nucleic acid encoding an HAS2 polypeptide operably linked to a promoter, wherein the rAAV comprises an AAV5 capsid, and wherein following administration the HAS2 polypeptide is expressed and catalyzes the production of additional hyaluronic acid, thereby increasing the level of hyaluronic acid (HA) in the canine, wherein the HAS2 polypeptide comprises the amino acid sequence set forth in SEQ ID NO:2.
Dependencies are inferred from the claim text.