Choi Vivian W, McCarty Douglas M, Samulski R Jude
Department of Pharmacology, University of North Carolina at Chapel Hill, NC 27599, USA.
Curr Gene Ther. 2005 Jun;5(3):299-310. doi: 10.2174/1566523054064968.
In recent years, significant efforts have been made on studying and engineering adeno-associated virus (AAV) capsid, in order to increase efficiency in targeting specific cell types that are non-permissive to wild type (wt) viruses and to improve efficacy in infecting only the cell type of interest. With our previous knowledge of the viral properties of the naturally occurring serotypes and the elucidation of their capsid structures, we can now generate capsid mutants, or hybrid serotypes, by various methods and strategies. In this review, we summarize the studies performed on AAV retargeting, and categorize the available hybrid serotypes to date, based on the type of modification: 1) transcapsidation, 2) adsorption of bi-specific antibody to capsid surface, 3) mosaic capsid, and 4) chimeric capsid. Not only these hybrid serotypes could achieve high efficiency of gene delivery to a specific targeted cell type, which can be better-tailored for a particular clinical application, but also serve as a tool for studying AAV biology such as receptor binding, trafficking and genome delivery into the nucleus.
近年来，人们在研究和改造腺相关病毒（AAV）衣壳方面付出了巨大努力，目的是提高靶向对野生型（wt）病毒不敏感的特定细胞类型的效率，并提高仅感染目标细胞类型的效力。基于我们对天然存在的血清型病毒特性的先前了解以及对其衣壳结构的阐明，我们现在可以通过各种方法和策略来生成衣壳突变体或杂交血清型。在这篇综述中，我们总结了对AAV重新靶向的研究，并根据修饰类型对迄今为止可用的杂交血清型进行分类：1）转衣壳化，2）双特异性抗体吸附到衣壳表面，3）镶嵌衣壳，4）嵌合衣壳。这些杂交血清型不仅可以实现高效的基因传递到特定的靶向细胞类型，从而可以更好地针对特定的临床应用进行定制，而且还可以作为研究AAV生物学的工具，例如受体结合、运输和基因组传递到细胞核。
