A User's Guide to the Inverted Terminal Repeats (ITR) of Adeno-Associated Virus.

Q1 Immunology and Microbiology

Human Gene Therapy Methods Pub Date : 2019-11-21 DOI:10.1089/hgtb.2019.276

Patrick Wilmott, L. Lisowski, I. Alexander, G. Logan

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引用次数: 18

Abstract

Ongoing development of recombinant vectors based on adeno-associated virus (rAAV) is providing an increasingly powerful and widely used toolkit for gene transfer and genome editing applications. While conceptually simple, the system harbours considerable complexity that presents many potential pitfalls for the inexperienced user. The short inverted terminal repeats (ITR) can prove to be particularly problematic during vector engineering due to inherent instability necessitating diligent quality control measures during vector manufacture. This is especially important from a clinical standpoint when consistent purity and potency are paramount, and all components of the system are rigorously scrutinized by regulatory agencies. Despite the discovery over thirty years ago that the AAV ITRs are the only cis-acting elements of the virus required for vector production, there is a scarcity of reviews specifically focused on these complex elements. This review provides an overview of the ITR with the dual purpose of acting as a user's guide in the application of AAV vector technology and as a roadmap for ongoing vector development and optimization.

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腺相关病毒的反向末端重复序列(ITR)用户指南。

基于腺相关病毒(rAAV)的重组载体的持续发展为基因转移和基因组编辑应用提供了越来越强大和广泛使用的工具包。虽然概念上很简单，但该系统具有相当的复杂性，对于没有经验的用户来说存在许多潜在的缺陷。短反向末端重复序列(ITR)由于其固有的不稳定性，在载体制造过程中需要采取严格的质量控制措施，因此在载体工程中尤其成问题。当始终如一的纯度和效力是最重要的，并且系统的所有组成部分都由监管机构严格审查时，从临床角度来看，这一点尤其重要。尽管早在30多年前就发现AAV itr是病毒产生病媒所需的唯一顺式作用元件，但专门关注这些复杂元件的综述却很少。本文综述了ITR的概况，其双重目的是作为AAV载体技术应用的用户指南，并作为正在进行的载体开发和优化的路线图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Gene Therapy Methods BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY

CiteScore

5.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases. The Journal is divided into three parts. Human Gene Therapy, the flagship, is published 12 times per year. HGT Methods, a bimonthly journal, focuses on the applications of gene therapy to product testing and development. HGT Clinical Development, a quarterly journal, serves as a venue for publishing data relevant to the regulatory review and commercial development of cell and gene therapy products.