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使用鼠逆转录病毒载体进行体内基因转移的效率在小鼠中具有品系依赖性。

Efficiency of in vivo gene transfer using murine retroviral vectors is strain-dependent in mice.

作者信息

Fassati A, Wells D J, Walsh F S, Dickson G

机构信息

Department of Biochemistry, Royal Holloway College, Egham, Surrey, UK.

出版信息

Hum Gene Ther. 1995 Sep;6(9):1177-83. doi: 10.1089/hum.1995.6.9-1177.

Abstract

Retroviral vectors can be used to transduce cultured cells at high frequencies, but efficient transduction of target cells in vivo has proved difficult and little is known about the factors that influence the efficiency of retroviral infection. Many commonly used mouse strains harbor endogenous C-type proviruses, some of which are expressed and have circulating antibodies against the viral envelope glycoproteins that cross-react with the Moloney strain of murine leukemia virus (MoMLV), from which most current retroviral vectors are derived. We have investigated the relative efficiency of retroviral-mediated gene transfer into regenerating skeletal muscle of a variety of mouse strains using a MoMLV-based vector. Humoral immune competence and interference between endogenous MLVs and exogenous recombinant MoMLV were observed to affect the efficiency of retroviral-mediated transfection in vivo. Our results indicate that the mouse genetic background and immune status need to be considered when choosing a preclinical model for in vivo retroviral-mediated gene transfer.

摘要

逆转录病毒载体可用于高效转导培养细胞,但在体内高效转导靶细胞已被证明很困难,而且对于影响逆转录病毒感染效率的因素知之甚少。许多常用的小鼠品系携带内源性C型前病毒,其中一些会表达,并且存在针对病毒包膜糖蛋白的循环抗体,这些抗体与莫洛尼氏小鼠白血病病毒(MoMLV)发生交叉反应,而目前大多数逆转录病毒载体都来源于MoMLV。我们使用基于MoMLV的载体研究了逆转录病毒介导的基因转移到多种小鼠品系再生骨骼肌中的相对效率。观察到体液免疫能力以及内源性MLV与外源性重组MoMLV之间的干扰会影响体内逆转录病毒介导的转染效率。我们的结果表明,在选择用于体内逆转录病毒介导基因转移的临床前模型时,需要考虑小鼠的遗传背景和免疫状态。

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