Center for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Nat Rev Cancer. 2011 Dec 1;12(1):51-8. doi: 10.1038/nrc3179.
Interactions between newly integrated DNA and the host genome limit the reliability and safety of transgene integration for therapeutic cell engineering and other applications. Although targeted gene delivery has made considerable progress, the question of where to insert foreign sequences in the human genome to maximize safety and efficacy has received little attention. In this Opinion article, we discuss 'genomic safe harbours' - chromosomal locations where therapeutic transgenes can integrate and function in a predictable manner without perturbing endogenous gene activity and promoting cancer.
新整合的 DNA 与宿主基因组之间的相互作用限制了转基因整合用于治疗性细胞工程和其他应用的可靠性和安全性。尽管靶向基因递送已经取得了相当大的进展,但在人类基因组中何处插入外源序列以最大程度地提高安全性和有效性的问题却很少受到关注。在这篇观点文章中,我们讨论了“基因组安全港”——治疗性转基因可以在不干扰内源性基因活性和促进癌症的情况下以可预测的方式整合和发挥功能的染色体位置。