Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector
Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector
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DOI：
10.1128/jvi.70.11.8098-8108.1996
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发表时间：
1996-11-01
影响因子：
5.4
通讯作者：
Samulski, RJ
中科院分区：
文献类型：
--
作者：
Xiao, XA;Li, JA;Samulski, RJ
肌肉定向基因转移正在考虑用于治疗几种代谢性疾病，包括血友病和Duchene肌营养不良症。先前用各种载体系统靶向该组织进行体细胞递送的努力已经导致瞬时表达，这是由于转基因的沉默或针对载体转导的细胞的免疫应答。我们将携带lacZ报告基因的重组腺相关病毒载体（rAAV）导入免疫活性小鼠的肌肉组织中。lacZ报告基因被有效地转导和表达，没有细胞免疫应答的证据。此外，基因表达持续超过1.5年。rAAV载体DNA的分子表征表明了持久性的机制，因为载体游离体转化为高分子量基因组DNA。这些数据提供了第一份报告，建立长期的基因转导到哺乳动物肌肉细胞在体内，而不需要免疫调节的有机体。
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.