Superior neovascularization and muscle regeneration in ischemic skeletal muscles following VEGF gene transfer by rAAV1 pseudotyped vectors.
Recombinant adeno-associated virus serotype 2 (rAAV2) vector has been widely employed for gene therapy. Recent progress suggests that the new serotypes of AAV showed a better performance than did AAV2 in normal tissues. Here, we evaluate the potential role of human vascular endothelial growth factor (VEGF) gene transfer using rAAV vector pseudotyped with serotype 1 capsid proteins (rAAV1) in the treatment of muscle ischemia. In ischemic skeletal muscles, the rAAV1-LacZ vector allowed higher level, broader distribution, and long-lasting gene expression compared with the rAAV2-LacZ vector. Muscle VEGF165 production following the rAAV1-VEGF165 vector injection was 5-10 times higher than that following the rAAV2-VEGF165 vector injection. VEGF165 production mediated by the rAAV1-VEGF165 vector stimulated a large set of neovascularization with relatively mature vascular structures and enhanced muscle regeneration in the ischemic skeletal muscles. Thus, the rAAV1-VEGF165 vector mediated gene transfer may be a therapeutic approach to peripheral vascular diseases.
Yan
Hua
H
Department of Cardiology, Peking University Third Hospital, No. 49, North Garden Road, Beijing 100083, China.
Guo
Yanhong
Y
Zhang
Peng
P
Zu
Lingyun
L
Dong
Xiaoyan
X
Chen
Li
L
Tian
Jianwei
J
Fan
Xiaolong
X
Wang
Nanping
N
Wu
Xiaobing
X
Gao
Wei
W
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018014:Gene Transfer Techniques; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011995:Recombination, Genetic; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A