1 Harvard Medical School, Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
2 University College London , Great Ormond Street Institute of Child Health, Faculty of Population Health Sciences, London, United Kingdom .
Hum Gene Ther. 2017 Dec;28(12):1122-1129. doi: 10.1089/hum.2017.183.
Integration site (IS) analysis is one of the major tools for addressing the safety of gene therapy clinical protocols based on the use of integrating vectors. Over the past years, the study of viral insertions in gene therapy-treated patients has allowed identifying insertional mutagenesis events, evaluating the safety of new viral vector platforms and tracking the in vivo clonal dynamics of genetically engineered cell products. While gene therapy is progressively expanding its impact on a broader area of clinical applications, increasingly more accessible, faster, and more reliable safety readouts are required from IS analysis. Several actors, from researchers to clinicians, from regulatory agencies to private companies, have to interface to different degrees with the results of IS analysis while developing and evaluating gene therapy products based on retroviral vectors. This review is aimed at providing a brief overview of what the current state and the future is of these studies with a particular focus on what are the main analytical constraints that should be considered upon conducting IS analysis in clinical gene therapy.
整合位点（IS）分析是基于整合载体的基因治疗临床方案安全性评估的主要工具之一。在过去的几年中，对基因治疗患者中病毒插入的研究已经允许鉴定插入突变事件，评估新型病毒载体平台的安全性，并跟踪基因工程细胞产品的体内克隆动力学。随着基因治疗逐渐扩大其对更广泛临床应用领域的影响，需要从整合位点分析中获得越来越多的可及性更高、更快、更可靠的安全性指标。在开发和评估基于逆转录病毒载体的基因治疗产品时，从研究人员到临床医生，从监管机构到私营公司的各个角色都必须在不同程度上与整合位点分析的结果进行对接。这篇综述旨在简要概述这些研究的现状和未来，特别关注在临床基因治疗中进行整合位点分析时应考虑的主要分析限制。
