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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Targeting lentiviral vectors to specific cell types in vivo
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Targeting lentiviral vectors to specific cell types in vivo

机译：将慢病毒载体靶向体内的特定细胞类型

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摘要

We have developed an efficient method to target lentivirus-mediated gene transduction to a desired cell type. It involves incorporation of antibody and fusogenic protein as two distinct molecules into the lentiviral surface. The fusogen is constructed by modifying viral envelope proteins, so that they lack the ability to bind to their cognate receptor but still retain the ability to trigger pH-dependent membrane fusion. Thus, the specificity of such a lentiviral vector is solely determined by the antibody, which is chosen to recognize a specific surface antigen of the desired cell type. This specific binding then induces endocytosis of the surface antigen, bringing the lentivirus into an endosome. There, the fusogen responds to the low pH environment and mediates membrane fusion, allowing the virus core to enter the cytosol. Using CD20 as a target antigen for human B cells, we have demonstrated that this targeting strategy is effective both in vitro and in intact animals. This methodology is flexible and can be extended to other forms of cell type-specific recognition to mediate targeting. The only requirement is that the antibody (or other binding protein) must be endocytosed after interaction with its cell surface-binding determinant.
机译：我们已经开发出一种有效的方法，可将慢病毒介导的基因转导靶向所需的细胞类型。它涉及将抗体和融合蛋白作为两个不同的分子掺入慢病毒表面。融合蛋白是通过修饰病毒包膜蛋白构建的，因此它们缺乏结合其同源受体的能力，但仍保留了触发pH依赖性膜融合的能力。因此，这种慢病毒载体的特异性仅由抗体决定，选择该抗体以识别所需细胞类型的特定表面抗原。然后这种特异性结合诱导表面抗原的内吞作用，将慢病毒带入内体。在那里，融合蛋白对低pH值环境做出反应并介导膜融合，从而使病毒核心进入细胞质。使用CD20作为人类B细胞的靶抗原，我们证明了这种靶向策略在体外和完整动物中均有效。该方法是灵活的，可以扩展到其他形式的细胞类型特异性识别，以介导靶向。唯一的要求是抗体（或其他结合蛋白）在与其细胞表面结合决定簇相互作用后必须被内吞。

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