Gene therapy studies in a canine model of X-linked severe combined immunodeficiency.
Gene therapy studies in a canine model of X-linked severe combined immunodeficiency.
复制标题
X连锁严重联合免疫缺陷犬模型的基因治疗研究。
DOI：
10.1089/humc.2015.004
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kiem,Hans-Peter
中科院分区：
文献类型：
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作者：
Felsburg,PeterJ;DeRavin,SukSee;Malech,HarryL;Sorrentino,BrianP;Burtner,Christopher;Kiem,Hans-Peter
自从在X连锁严重联合免疫缺陷（XSCID）的原始人类γ-逆转录病毒基因治疗试验中出现T细胞白血病以来，人们一直致力于开发更安全的载体。本文综述了在犬XSCID模型中进行的基因治疗研究，以评估γ-逆转录病毒、慢病毒和泡沫病毒载体治疗XSCID的疗效，以及一种新的载体递送方法。这些研究表明，持久的T细胞重建和胸腺生成没有任何严重不良事件的证据，并且与人XSCID患者相反，可以在没有任何预处理条件下实现长达5年的骨髓细胞和B细胞中的持续标记以及正常体液免疫功能的重建。基因标记的T细胞、B细胞和更重要的髓样细胞的持续水平存在几乎5年，这高度提示多能造血干细胞或非常原始的定向祖细胞的转导。
Since the occurrence of T cell leukemias in the original human γ-retroviral gene therapy trials for X-linked severe combined immunodeficiency (XSCID), considerable effort has been devoted to developing safer vectors. This review summarizes gene therapy studies performed in a canine model of XSCID to evaluate the efficacy of γ-retroviral, lentiviral, and foamy viral vectors for treating XSCID and a novel method of vector delivery. These studies demonstrate that durable T cell reconstitution and thymopoiesis with no evidence of any serious adverse events and, in contrast to the human XSCID patients, sustained marking in myeloid cells and B cells with reconstitution of normal humoral immune function can be achieved for up to 5 years without any pretreatment conditioning. The presence of sustained levels of gene-marked T cells, B cells, and more importantly myeloid cells for almost 5 years is highly suggestive of transduction of either multipotent hematopoietic stem cells or very primitive committed progenitors.