Intramuscular and Intravenous AAV-Mediated Gene Delivery in Mouse Models.

Abstract

Recombinant adeno-associated virus (rAAV)-mediated gene therapy is a powerful approach for precise delivery of desired eukaryotic genes to a wide range of target cells and tissues to treat various types of muscular and neuromuscular diseases, including spinal muscular atrophy, Duchenne/Becker muscular dystrophy (DMD/BMD), and limb-girdle muscular dystrophy.Proof-of-concept, preclinical, and clinical studies in these and other fields have demonstrated high transduction efficiency of naturally occurring and engineered rAAV serotypes across multiple mammalian species, from rodents and dogs to nonhuman primates and humans, to target skeletal muscles, heart, diaphragm, and central nervous system via various routes of administration. Among them, intramuscular and intravenous injections are the most widely used routes for administering therapeutic molecules such as rAAV vector particles in dystrophic animals.The protocols compiled in this chapter describe a simple, reliable, and reproducible method for injecting rAAV vectors using both administration techniques to deliver genes of interest into neonates and adult mice to study muscular and neuromuscular diseases and develop therapeutic options for their treatment.