Abstract: The paper generated a modified AAV serotype, named AAVc1, by inserting an oligopeptide PGPSPAD after N573 of the AAV5 capsid, which exhibited better muscle tropism than AAV5, 8 and 9 both in vitro and in vivo. The number of green fluorescence protein (GFP) positive C2C12 myoblast cells in AAVc1 group was 25% higher than AAV9 group, almost twice the AAV8 group and three times of the AAV5 group. The percentage of both type I and type II skeletal muscle fibers infected by AAVc1 was also 20% −30% higher than those infected by AAV9, implicating better transduction efficiency of AAVc1 in murine muscles. Furthermore, we found that neutralizing antibodies (Nabs) present in rhesus monkey sera against AAVc1 were less than those against AAV9, indicating its less immune response against AAVc1 than AAV9. Altogether, these observations illuminate potential advantages of AAVc1 over wild type AAV serotypes for gene therapy.