遗传增强
腺相关病毒
基因传递
生物
载体(分子生物学)
杜氏肌营养不良
骨骼肌
基因
免疫学
病毒载体
解剖
遗传学
重组DNA
作者
Zhong Wang,Tong Zhu,Chunming Qiao,Lei Zhou,Bing Wang,Jian Zhang,Chunlian Chen,Juan Li,Xiao Xiao
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 AAV1 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.
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