Somia N V, Zoppé M, Verma I M
Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, San Diego, CA 92186-5800, USA.
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7570-4. doi: 10.1073/pnas.92.16.7570.
We report the generation of a retroviral vector that infects human cells specifically through recognition of the low density lipoprotein receptor. The rationale for this targeted infection is to add onto the ecotropic envelope protein of Moloney murine leukemia virus, normally trophic for murine cells, a single-chain variable fragment derived from a monoclonal antibody recognizing the human low density lipoprotein receptor. This chimeric envelope protein was used to construct a packaging cell line producing a retroviral vector capable of high-efficiency transfer of the Escherichia coli beta-galactosidase gene to human cells expressing low density lipoprotein receptor. This approach offers a generalized plan to generate cell and tissue-specific retroviral vectors, an essential step toward in vivo gene therapy strategies.
我们报道了一种逆转录病毒载体的构建，该载体通过识别低密度脂蛋白受体特异性感染人类细胞。这种靶向感染的原理是，在莫洛尼鼠白血病病毒的嗜亲性包膜蛋白（通常对鼠细胞具有嗜性）上，添加一个源自识别人类低密度脂蛋白受体的单克隆抗体的单链可变片段。这种嵌合包膜蛋白被用于构建一个包装细胞系，该细胞系可产生一种逆转录病毒载体，能够将大肠杆菌β-半乳糖苷酶基因高效转移至表达低密度脂蛋白受体的人类细胞。此方法提供了一个构建细胞和组织特异性逆转录病毒载体的通用方案，这是迈向体内基因治疗策略的关键一步。
