Gene therapy in golden retriever muscular dystrophy model

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Gene therapy in golden retriever muscular dystrophy model This project will focus on the DMD dog model (GRMD) to investigate blood-vessel-mediated gene delivery of AAV vectors into the limbs and eventually the wholedody. Specific Aim 1 is designed to compare regional gene delivery efficiency of arterial and venous methods in the limbs. Arterial delivery with pressure and/or with vessel dilators was investigated in early studies by a few labs. But more recent studies have switched to the pressurized intravenous delivery methods. However, a latest report revived the arterial method again, but without the use of any additional pressure and drugs. These methods have their pros and cons, but are never compared side-by-side. In Aim 1 we propose to compare and optimize the regional AAV vector delivery methods in dog limbs. Specific Aim 2 is designed to examine systemic gene delivery efficiency of AAV8 and AAV9 in dogs. Previously we and others have shown that new serotypes of AAV can achieve wholebody gene delivery by simple intravenous injection in mice and hamsters. In Aim 2, we plan to explore both AAV8 and AAV9 for systemic gene delivery in the dogs. We will also examine any novel AAV vectors yielded by Project 2.