Engineered Viruses as Genome Editing Devices.
Engineered Viruses as Genome Editing Devices.
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DOI：
10.1038/mt.2015.164
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Gonçalves MA
中科院分区：
文献类型：
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作者：
Chen X;Gonçalves MA
基于序列特异性设计核酸酶（也称为可编程核酸酶）的基因组编辑试图以靶向和精确的方式修改活细胞的遗传信息内容。将设计者核酸酶单独或与用作替代同源重组（HR）底物的供体DNA模板一起递送到细胞中可分别导致基因敲除或基因敲入。作为工程化的复制缺陷型病毒，病毒载体作为供体DNA模板和设计核酸酶的递送载体具有越来越重要的作用，所述设计核酸酶即锌指核酸酶（ZFN）、转录激活因子样效应物核酸酶（TALEN）和成簇的、规则间隔的短回文重复序列（CRISPR）相关的Cas9（CRISPR-Cas9）核酸酶，也称为RNA引导的核酸酶（RGN）。我们回顾了工程病毒颗粒在基因组编辑中发挥的双重作用，同时关注其主要支架，包括慢病毒，腺相关病毒和腺病毒。此外，越来越多的关于病毒载体作为基因组编辑工具的传递系统的研究的覆盖面，补充了有关其主要特征，优点和缺点的信息。最后，这些信息是通过对整个基因组编辑领域的主要原理，工具和应用的简明描述来构建的。
Genome editing based on sequence-specific designer nucleases, also known as programmable nucleases, seeks to modify in a targeted and precise manner the genetic information content of living cells. Delivering into cells designer nucleases alone or together with donor DNA templates, which serve as surrogate homologous recombination (HR) substrates, can result in gene knockouts or gene knock-ins, respectively. As engineered replication-defective viruses, viral vectors are having an increasingly important role as delivery vehicles for donor DNA templates and designer nucleases, namely, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated Cas9 (CRISPR−Cas9) nucleases, also known as RNA-guided nucleases (RGNs). We review this dual role played by engineered viral particles on genome editing while focusing on their main scaffolds, consisting of lentiviruses, adeno-associated viruses, and adenoviruses. In addition, the coverage of the growing body of research on the repurposing of viral vectors as delivery systems for genome editing tools is complemented with information regarding their main characteristics, pros, and cons. Finally, this information is framed by a concise description of the chief principles, tools, and applications of the genome editing field as a whole.