Systemic Delivery of Adeno-Associated Viral Vectors in Mice and Dogs
Many diseases affect multiple tissues and/or organ systems, or affect tissues that are broadly distributed. For these diseases, an effective gene therapy will require systemic delivery of the therapeutic vector to all affected locations. Adeno-associated virus (AAV) has been used as a gene therapy vector for decades in preclinical studies and human trials. These studies have shown outstanding safety and efficacy of the AAV vector for gene therapy. Recent studies have revealed yet another unique feature of the AAV vector. Specifically, AAV can lead to bodywide gene transfer following a single intravascular injection. Here we describe the protocols for effective systemic delivery of AAV in both neonatal and adult mice and dogs. We also share lessons we learned from systemic gene therapy in the murine and canine models of Duchenne muscular dystrophy.
Key wordsDMD Systemic delivery AAV Neonatal mice Neonatal dogs Adult mice Adult dogs
The research on systemic AAV delivery in the Duan lab was supported by the National Institutes of Health (NS-90634, AR-70517 and AR-69085 ), Department of Defense (MD150133), Jesse’s Journey-The Foundation for Gene and Cell Therapy, Hope for Javier, Jackson Freel DMD Research Fund and Solid Biosciences Inc. The authors thank Keqing Zhang for the assistance in figure preparation.
Disclosure: D.D. is a member of the scientific advisory board, an equity holder of Solid Biosciences, LLC. D.D. is an inventor on a patent licensed to Solid Biosciences, LLC.
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