1. ¹Department of Neurology and Senator D. Paul, Wellstone Muscular Dystrophy Cooperative Research Center
2. ²Department of Medicine and Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA
3. ³Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

Correspondence: Jeffrey S. Chamberlain, University of Washington School of Medicine, 1959 NE Pacific Street, HSB K243, Seattle, WA 98195-7720, USA. Fax: (206) 616 8272. E-mail: Jsc5@u.washington.edu

^*These authors contributed equally to this work.

Received 21 June 2004; Revised 10 July 2004; Accepted 13 July 2004.

Abstract

Vectors based on recombinant adeno-associated viruses (rAAV) have emerged as tools of choice for gene transfer to skeletal muscle. rAAV vectors demonstrate efficient, safe, and stable transduction. Multiple serotypes of AAV exist, but vectors based on serotype 2 (rAAV2) are the most thoroughly characterized and frequently employed. Here, we characterize transduction of the skeletal musculature using rAAV vectors pseudotyped with serotype 6 capsid proteins (rAAV6). We demonstrate that rAAV6 vectors can efficiently transduce the skeletal musculature of mice at levels >500-fold higher than is achievable with rAAV2 vectors and can readily saturate individual muscles following direct injection. Further, rAAV6 vectors are capable of transducing the diaphragm and intercostal muscles of mice after a simple injection into the intrathoracic cavity and are capable of widespread transduction throughout the musculature of mice injected in the intraperitoneal space as newborn pups. These results demonstrate that rAAV6 vectors hold great potential for use in gene delivery protocols targeting the skeletal musculature.