Transduction efficiency of AAV serotypes after local injection in mouse and human skeletal muscle.

Adeno-associated viral vector (AAV) is an efficient tool for gene delivery in skeletal muscle. AAV-based therapies show promising results for the treatment of various genetic disorders, including muscular dystrophies. These dystrophies represent an heterogeneous group of diseases affecting muscles and typically characterized by progressive skeletal muscle wasting and weakness and the development of fibrosis. The tropism of each AAV serotype has been extensively studied using systemic delivery routes, but very few studies have compared their transduction efficiency via direct intramuscular injection. Yet, in some muscular dystrophies, where only a few muscles are primarily affected, a local intramuscular injection to target these muscles would be the most appropriate route. A comprehensive comparison between different rAAV serotypes is therefore needed. Here, we investigated the transduction efficiency of rAAV serotypes 1 to 10 by local injection in skeletal muscle of control C57BL/6 mice. We used a CMV-nls-LacZ reporter cassette allowing nuclear expression of LacZ to easily localize targeted cells. Detection of beta-galactosidase activity on muscle cryo-sections demonstrated that rAAV1, 7, 8, 9 and 10 were more efficient than the others with rAAV9 being the most efficient in mouse. Furthermore, using a model of human muscle xenograft in immunodeficient mice, we observed that in human muscle rAAV8 and rAAV9 had similar transduction efficiency. These findings demonstrate for the first time that human muscle xenograft can be used to evaluate AAV-based therapeutical approaches in a human context.