Efficacy of recombinant adeno-associated virus vectors with different serotypes in the transduction of mature muscle fibers

Objective Recombinant vectors based on 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 (rAAV-2) are the most thoroughly characterized and frequently employed. Here, we investigate the role of rAAV vectors with other different serotypes in the transduction of mature skeletal muscle fibers. Methods rAAV vectors of different serotypes (rAAV-1, rAAV-2, rAAV-3 and rAAV-5) that express the report gene LacZ or GDNF were adopted to investigate the transduction efficacy of slow or fast skeletal muscle fibers. The transgene expression was evaluated by histochemical method or ELISA. Results In 3-week old mice, histochemical staining for LacZ showed that rAAV5 efficiently transduced both slow and fast myofibers while slow fibers were preferentially transduced by rAAV2 and rAAV3. In 8-week old (adult) mice, rAAV3 and rAAV5 efficiently transduced both slow and fast myofibers. Preferential transduction of slow myofibers with rAAV3-lacZ or with rAAV5-lacZ was not remarkable in contrast to transduction with rAAV2-lacZ. We also explored the gene expression of intramuscular delivery of the GDNF gene mediated by rAAVs in 8-week old mice. rAAV1-GDNF is the most efficient serotype for the expression. rAAV-2, rAAV-3 and rAAV5 were demonstrated also efficient for transgene expression in skeletal muscle. Conclusion These results demonstrate that rAAV-3 and rAAV-5 vectors hold great potential for use in gene delivery protocols targeting the skeletal musculature.