Farinelli Giada, Capo Valentina, Scaramuzza Samantha, Aiuti Alessandro
Department of Pediatrics, Children's Hospital Bambino Gesù and University of Rome Tor Vergata School of Medicine, Rome, Italy.
J Inherit Metab Dis. 2014 Jul;37(4):525-33. doi: 10.1007/s10545-014-9690-y. Epub 2014 Mar 12.
In the last years important progress has been made in the treatment of several primary immunodeficiency disorders (PIDs) with gene therapy. Hematopoietic stem cell (HSC) gene therapy indeed represents a valid alternative to conventional transplantation when a compatible donor is not available and recent success confirmed the great potential of this approach. First clinical trials performed with gamma retroviral vectors were promising and guaranteed clinical benefits to the patients. On the other hand, the outcome of severe adverse events as the development of hematological abnormalities highlighted the necessity to develop a safer platform to deliver the therapeutic gene. Self-inactivating (SIN) lentiviral vectors (LVVs) were studied to overcome this hurdle through their preferable integration pattern into the host genome. In this review, we describe the recent advancements achieved both in vitro and at preclinical level with LVVs for the treatment of Wiskott-Aldrich syndrome (WAS), chronic granulomatous disease (CGD), ADA deficiency (ADA-SCID), Artemis deficiency, RAG1/2 deficiency, X-linked severe combined immunodeficiency (γchain deficiency, SCIDX1), X-linked lymphoproliferative disease (XLP) and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.
在过去几年中，基因治疗在几种原发性免疫缺陷疾病（PID）的治疗方面取得了重要进展。当无法获得相容供体时，造血干细胞（HSC）基因治疗确实是传统移植的一种有效替代方法，最近的成功证实了这种方法的巨大潜力。用γ逆转录病毒载体进行的首批临床试验很有前景，并为患者带来了临床益处。另一方面，诸如血液学异常发展等严重不良事件的结果凸显了开发更安全的治疗基因递送平台的必要性。研究了自失活（SIN）慢病毒载体（LVV），以通过其更优的整合模式进入宿主基因组来克服这一障碍。在本综述中，我们描述了LVV在体外和临床前水平上治疗威斯科特-奥尔德里奇综合征（WAS）、慢性肉芽肿病（CGD）、腺苷脱氨酶缺乏症（ADA-SCID）、阿耳忒弥斯缺乏症、RAG1/2缺乏症、X连锁严重联合免疫缺陷（γ链缺乏症，SCIDX1）、X连锁淋巴增殖性疾病（XLP）以及免疫失调、多内分泌腺病、肠病、X连锁（IPEX）综合征方面取得的最新进展。
