摘要
最近基础和临床研究工作都表明锌指核酸酶(ZFNs),CRISPR/Cas9,和其他可编程的特定位点的核酸内切酶技术被成功地运用到腺相关病毒(AAV)载体诱导人类染色体内定向基因编辑与治疗相关的水平。过去几十年的研究里,AAV载体基因组被认为是为同源性定向修复宿主基因组内存在或缺失的靶向的DNA损伤而增加的基质。另外,在研究不同的疾病的超过 100个临床试验中,AAV载体是目前在体内基因传递的最有效的形式,而且没有载体相关的并发症。同时,定制工程特异位点的核酸内切酶设计的进步和阐明核酸内切酶格式的运用导致了为基础科学和临床治疗的高效、便捷的遗传工程。腺相关病毒载体和基因编辑技术明显的结合,可利用AAV作为修复底物和/或编码设计内切酶基因的传递;然而,当有效的递送和通过载体基因组提高基因定位有利时,AAV载体的其他特性对基因编辑技术不可取。本文综述了AAV载体在基因编辑技术起到多方面的作用,提供了其对遗传疾病的治疗趋势的见解。
关键词: 腺相关病毒的载体作用,DSB, CRISPR/Cas9, DNA,锌指核酸酶。
Current Gene Therapy
Title:AAV Vectorization of DSB-mediated Gene Editing Technologies
Volume: 16 Issue: 3
Author(s): Rachel J. Moser, Matthew L. Hirsch
Affiliation:
关键词: 腺相关病毒的载体作用,DSB, CRISPR/Cas9, DNA,锌指核酸酶。
摘要: Recent work both at the bench and the bedside demonstrate zinc-finger nucleases (ZFNs), CRISPR/Cas9, and other programmable site-specific endonuclease technologies are being successfully utilized within and alongside AAV vectors to induce therapeutically relevant levels of directed gene editing within the human chromosome. Studies from past decades acknowledge that AAV vector genomes are enhanced substrates for homology-directed repair in the presence or absence of targeted DNA damage within the host genome. Additionally, AAV vectors are currently the most efficient format for in vivo gene delivery with no vector related complications in >100 clinical trials for diverse diseases. At the same time, advancements in the design of custom-engineered site-specific endonucleases and the utilization of elucidated endonuclease formats have resulted in efficient and facile genetic engineering for basic science and for clinical therapies. AAV vectors and gene editing technologies are an obvious marriage, using AAV for the delivery of repair substrate and/or a gene encoding a designer endonuclease; however, while efficient delivery and enhanced gene targeting by vector genomes are advantageous, other attributes of AAV vectors are less desirable for gene editing technologies. This review summarizes the various roles that AAV vectors play in gene editing technologies and provides insight into its trending applications for the treatment of genetic diseases.
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Cite this article as:
Rachel J. Moser, Matthew L. Hirsch , AAV Vectorization of DSB-mediated Gene Editing Technologies, Current Gene Therapy 2016; 16 (3) . https://dx.doi.org/10.2174/1566523216666160602213738
DOI https://dx.doi.org/10.2174/1566523216666160602213738 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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