GFP Adeno-Associated Virus ( AAV588MTP )

Gene therapy is an effective strategy for treating a variety of muscle diseases, such as muscular dystrophy and heart failure. Gene transfer vectors, both non-viral and viral, have been shown to deliver genes to local muscle and cardiac tissues via direct intramuscular (i.m.) injection or local vascular perfusion. The simplest approach to gene therapy is to inject naked plasmid DNA encoding the therapeutic gene into the muscle. Although plasmid DNA delivery can achieve long-term gene expression, naked plasmid delivery efficiency is low after intramuscular injection. Viral vectors, especially AAV vectors, provide an effective alternative for muscle-directed gene transfer. One of the approaches to target AAV to muscle is to alter its natural interaction with cellular receptors and retarget the virus to muscle via different binding ligands. Among the AAV serotypes currently in use, AAV2 is the serotype with the best characterized virus-cell interactions. To improve muscle tropism, a 7-amino acid (ASSLNIA) muscle targeting peptide (MTP) can be inserted at residue 588 of the AAV2 capsid to generate AAV588MTP. In cultured cells, the insertion of the MTP not only conferred AAV2 infectivity to differentiated myotubes, but also abolished or impaired its infectivity to other permissive non-muscle cells. Furthermore, the insertion of the MTP at capsid position 588 was able to enhance the infectivity of AAV2 to muscle myofibers in vivo by 3.2-fold after intramuscular injection.