基于逆转录病毒的重症联合免疫缺陷（SCID）矫正策略。

Strategies for retrovirus-based correction of severe, combined immunodeficiency (SCID).

作者信息

Fischer Alain, Hacein-Bey-Abina Salima, Cavazzana-Calvo Marina

机构信息

Descartes University of Paris, Paris, France.

出版信息

Methods Enzymol. 2012;507:15-27. doi: 10.1016/B978-0-12-386509-0.00002-8.

DOI:10.1016/B978-0-12-386509-0.00002-8

PMID:22365767

Abstract

Severe combined immunodeficiencies (SCIDs) appear as optimal disease targets to challenge potential efficacy of gene therapy. Ex vivo, retrovirally mediated gene transfer into hematopoietic progenitor cells has been shown to provide sustained correction of two forms of SCID, that is, SCID-X1 and adenosine deaminase deficiencies. In the former case, however, genotoxicity was observed in a minority of patients as a consequence of retroviral integration into proto-oncogenes loci and transactivation. Design of vectors in which the enhancer element of retroviral LTR has been deleted and an internal promoter added (self-inactivated vectors) could provide both safe and efficient gene transfer as being presently tested.

摘要

重症联合免疫缺陷症（SCIDs）似乎是检验基因治疗潜在疗效的理想疾病靶点。体外实验表明，逆转录病毒介导的基因转移至造血祖细胞可使两种形式的SCID，即X1型SCID和腺苷脱氨酶缺陷得到持续纠正。然而，在前一种情况下，由于逆转录病毒整合到原癌基因位点并发生反式激活，少数患者出现了基因毒性。目前正在测试的一种载体设计是删除逆转录病毒长末端重复序列（LTR）的增强子元件并添加内部启动子（自失活载体），这种设计可实现安全有效的基因转移。