Papapetrou Eirini P, Schambach Axel
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mol Ther. 2016 Apr;24(4):678-84. doi: 10.1038/mt.2016.38. Epub 2016 Feb 12.
Genomic safe harbors (GSHs) are sites in the genome able to accommodate the integration of new genetic material in a manner that ensures that the newly inserted genetic elements: (i) function predictably and (ii) do not cause alterations of the host genome posing a risk to the host cell or organism. GSHs are thus ideal sites for transgene insertion whose use can empower functional genetics studies in basic research and therapeutic applications in human gene therapy. Currently, no fully validated GSHs exist in the human genome. Here, we review our formerly proposed GSH criteria and discuss additional considerations on extending these criteria, on strategies for the identification and validation of GSHs, as well as future prospects on GSH targeting for therapeutic applications. In view of recent advances in genome biology, gene targeting technologies, and regenerative medicine, gene insertion into GSHs can potentially catalyze nearly all applications in human gene therapy.
基因组安全位点（GSHs）是基因组中的一些位点，能够以确保新插入的遗传元件具备以下特性的方式容纳新遗传物质的整合：（i）可预测地发挥功能；（ii）不会导致宿主基因组发生改变从而对宿主细胞或生物体构成风险。因此，GSHs是转基因插入的理想位点，其应用能够推动基础研究中的功能遗传学研究以及人类基因治疗中的治疗应用。目前，人类基因组中不存在经过充分验证的GSHs。在此，我们回顾我们之前提出的GSH标准，并讨论在扩展这些标准、GSH鉴定和验证策略以及GSH靶向治疗应用的未来前景方面的其他考虑因素。鉴于基因组生物学、基因靶向技术和再生医学的最新进展，将基因插入GSHs有可能催化人类基因治疗中的几乎所有应用。
