San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, San Raffaele Scientific Institute, Milan, Italy.
Curr Opin Immunol. 2012 Oct;24(5):585-91. doi: 10.1016/j.coi.2012.07.012. Epub 2012 Aug 18.
Gene therapy has become an attractive alternative therapeutic strategy to allogeneic transplant for primary immunodeficiencies (PIDs) owing to known genetic defects. Clinical trials using gammaretroviral vectors have demonstrated the proof of principle of gene therapy for Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD), but have also highlighted limitations of the technology. New strategies based on vectors that can achieve more robust correction with less risk of insertional mutagenesis are being developed. In this review we present the status of gene therapy for WAS and CGD, and discuss the emerging application of similar strategies to a broader range of PIDs, such as IPEX syndrome.
基因治疗已成为原发性免疫缺陷症(PIDs)除同种异体移植外的一种有吸引力的治疗策略,因为其病因是已知的遗传缺陷。使用γ逆转录病毒载体的临床试验已经证明了基因治疗对 Wiskott-Aldrich 综合征(WAS)和慢性肉芽肿病(CGD)的原理,但也突出了该技术的局限性。正在开发基于能够实现更稳健校正且插入突变风险更低的载体的新策略。在这篇综述中,我们介绍了 WAS 和 CGD 的基因治疗现状,并讨论了类似策略在更广泛的 PID 中的新兴应用,如 IPEX 综合征。