Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart

被引:473
作者
Wang, Z
Zhu, T
Qiao, CP
Zhou, LQ
Wang, B
Zhang, J
Chen, CL
Li, J
Xiao, X
机构
[1] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Sch Med, Dept Orthoped Surg, Pittsburgh, PA 15261 USA
关键词
D O I
10.1038/nbt1073
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. Previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. We compared the efficiency of multiple adeno-associated virus (AAV) vectors after a single injection via intraperitoneal or intravenous routes without additional intervention. We show that AAV8 is the most efficient vector for crossing the blood vessel barrier to attain systemic gene transfer in both skeletal and cardiac muscles of mice and hamsters. Serotypes such as AM and AAV6, which demonstrate robust infection in skeletal muscle cells, were less effective in crossing the blood vessel barrier. Gene expression persisted in muscle and heart, but diminished in tissues undergoing rapid cell division, such as neonatal liver. This technology should prove useful for muscle-directed systemic gene therapy.
引用
收藏
页码:321 / 328
页数:8
相关论文
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