San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Pediatric Immunohematology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
Mol Ther. 2021 Feb 3;29(2):489-504. doi: 10.1016/j.ymthe.2020.11.020. Epub 2020 Nov 20.
Gene transfer into autologous hematopoietic stem progenitor cells (HSPCs) has the potential to cure monogenic inherited disorders caused by an altered development and/or function of the blood system, such as immune deficiencies and red blood cell and platelet disorders. Gene-corrected HSPCs and their progeny can also be exploited as cell vehicles to deliver molecules into the circulation and tissues, including the central nervous system. In this review, we focus on the progress of clinical development of medicinal products based on HSPCs engineered and modified by integrating viral vectors for the treatment of monogenic blood disorders and metabolic diseases. Two products have reached the stage of market approval in the EU, and more are foreseen to be approved in the near future. Despite these achievements, several challenges remain for HSPC gene therapy (HSPC-GT) precluding a wider application of this type of gene therapy to a wider set of diseases while gene-editing approaches are entering the clinical arena.
基因转移到自体造血干祖细胞（HSPCs）有可能治愈由血液系统发育和/或功能改变引起的单基因遗传性疾病，如免疫缺陷以及红细胞和血小板疾病。基因修正的 HSPCs 及其后代也可以作为细胞载体将分子递送到循环和组织中，包括中枢神经系统。在这篇综述中，我们重点介绍了基于整合病毒载体的 HSPCs 工程和修饰的治疗单基因血液疾病和代谢疾病的药物产品的临床开发进展。有两种产品已经达到欧盟市场批准的阶段，预计在不久的将来还会有更多的产品获得批准。尽管取得了这些成就，但 HSPC 基因治疗（HSPC-GT）仍然存在一些挑战，这限制了这种基因治疗更广泛地应用于更广泛的疾病范围，而基因编辑方法正进入临床领域。
