Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK.
Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
Hum Mol Genet. 2019 Oct 1;28(R1):R15-R23. doi: 10.1093/hmg/ddz170.
Gene therapy is now being trialled as a therapeutic option for an expanding number of conditions, based primarily on the successful treatment over the past two decades of patients with specific primary immunodeficiencies (PIDs) including severe combined immunodeficiency and Wiskott-Aldrich syndrome and metabolic conditions such as leukodystrophy. The field has evolved from the use of gammaretroviral vectors to more sophisticated lentiviral platforms that offer an improved biosafety profile alongside greater efficiency for hematopoietic stem cells gene transfer. Here we review more recent developments including licensing of gene therapies, use of gene corrected autologous T cells as an alternative strategy for some PIDs and the potential of targeted gene correction using various gene editing platforms. Given the promising results of recent clinical trials, it is likely that autologous gene therapies will become standard of care for a number of devastating diseases in the coming decade.
基因治疗目前正被作为越来越多疾病的治疗选择进行试验，这主要基于过去二十年中对特定原发性免疫缺陷病（PID）患者的成功治疗，包括严重联合免疫缺陷病和 Wiskott-Aldrich 综合征，以及代谢性疾病如脑白质营养不良。该领域已从使用γ逆转录病毒载体发展到更复杂的慢病毒平台，这些平台提供了更好的生物安全性，同时提高了造血干细胞基因转移的效率。在这里，我们回顾了最近的一些发展，包括基因治疗的许可、使用基因校正的自体 T 细胞作为某些 PID 的替代策略，以及利用各种基因编辑平台进行靶向基因校正的潜力。鉴于最近临床试验的可喜结果，在未来十年中，自体基因治疗很可能成为许多毁灭性疾病的标准治疗方法。
