Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector

作者：Xiao Xiao, Jing Li, R. Jude Samulski · 发表于：Journal of Virology · 年份：1996 · DOI：10.1128/jvi.70.11.8098-8108.1996 · 被引用次数：916 · 研究领域：Virus-based gene therapy research、Viral Infectious Diseases and Gene Expression in Insects、Viral Infections and Immunology Research

Muscle-directed gene transfer is being considered for the treatment of several metabolic diseases, including hemophilia and Duchene's muscular dystrophy. Previous efforts to target this tissue for somatic delivery with various vector systems have resulted in transient expression due to silencing of the transgene or to an immune response against the vector-transduced cells. We introduced recombinant adeno-associated virus vector (rAAV) carrying a lacZ reporter into muscle tissue of immunocompetent mice. The lacZ reporter gene was efficiently transduced and expressed with no evidence of a cellular immune response. Moreover, gene expression persisted for more than 1.5 years. Molecular characterization of rAAV vector DNA suggests a mechanism for persistence, since vector episomes convert to high-molecular-weight genomic DNA. These data provide the first report for establishing long-term gene transduction into mammalian muscle cells in vivo without the need for immune modulation of the organism.