Versatile targeting system for lentiviral vectors involving biotinylated targeting molecules.
Versatile targeting system for lentiviral vectors involving biotinylated targeting molecules.
复制标题
涉及生物素化靶向分子的慢病毒载体的多功能靶向系统。
DOI：
10.1016/j.virol.2018.09.017
复制
发表时间：
2018-12
期刊：
影响因子：
3.7
通讯作者：
Morizono K
中科院分区：
文献类型：
--
作者：
Situ K;Chua BA;Bae SY;Meyer AS;Morizono K
将某些类型的慢病毒载体与靶向配体结合可以将载体重新定向到特定的转导所需的细胞类型。然而，接合需要大量的遗传和/或生化操作，这阻碍了靶向慢病毒载体在更广泛的研究领域的应用。我们开发了与生物素结合分子融合的包膜蛋白，通过简单的混合将假类型载体与生物素化的靶向分子偶联。包膜蛋白与生物素结合的单体分子融合，而不是与四聚体分子融合，可以伪型慢病毒载体，并与生物素化的靶向配体结合。这种结合足够稳定，可以在有血清存在的情况下重定向慢病毒转导，表明它们在体内的潜力。当信号分子与载体结合时，这种结合以受体特异性的方式促进转导和信号传递。这种简单的配体偶联方法和容易获得各种类型的生物素化配体将使靶向慢病毒转导很容易应用于广泛的研究领域。
Conjugating certain types of lentiviral vectors with targeting ligands can redirect the vectors to specifically transduce desired cell types. However, extensive genetic and/or biochemical manipulations are required for conjugation, which hinders applications for targeting lentiviral vectors for broader research fields. We developed envelope proteins fused with biotin-binding molecules to conjugate the pseudotyped vectors with biotinylated targeting molecules by simply mixing them. The envelope proteins fused with the monomeric, but not tetrameric, biotin-binding molecules can pseudotype lentiviral vectors and be conjugated with biotinylated targeting ligands. The conjugation is stable enough to redirect lentiviral transduction in the presence of serum, indicating their potential in in vivo. When a signaling molecule is conjugated with the vector, the conjugation facilitates transduction and signaling in a receptor-specific manner. This simple method of ligand conjugation and ease of obtaining various types of biotinylated ligands will make targeted lentiviral transduction easily applicable to broad fields of research.
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