慢病毒载体转录“通读”改进研究进展

Progress in improvement of lentiviral vectors′ transcriptional read-through

摘要:

自2002年以来，在用γ-逆转录病毒载体治疗X连锁重度复合性免疫缺陷病 (X-SCID) 的10例病人中已有4例因载体整合在原癌基因lmo2等附近而得了白血病。这一事件提高了人们对基因治疗载体安全性的关注。与γ-逆转录病毒载体相比，慢病毒载体因尚未发现有整合在lmo2附近的现象，被认为是安全性较好的基因治疗载体。然而自灭活慢病毒载体与γ-逆转录病毒载体一样存在着转录“通读”的现象。近些年来，科学家们在改善自灭活慢病毒载体的通读率上做了一些工作并取得了一些积极成果。以下对慢病毒载体转录“通读”现象的发生机理和解决途径作了综合描述。

Abstract:

Four out of 10 patients of X-linked severe combined immunodeficiency (X-SCID) were finally developed leukemia after receiving the treatment of gene therapy delivered by γ-retroviral vectors. This is due to the vector integrated to the proximity of lmo2 etc proto-oncogene promoters, leading to the activation of onco-gene expression, which raises the concern of the bio-safety of gene therapy vectors. Lentiviral vectors, especially self-inactivating lentiviral vectors, are considered to be much safer than γ-retroviral vectors. However self-inactivating lentiviral vectors also have encountered with some unsafe factors and one of them is the problem of transcriptional “read-through”. During the past years, achievements have been made to reduce lentiviral vector transcriptional read-through, which are reviewed herein.