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基因治疗是近年迅速发展的一种治疗方式,目前制约基因治疗发展的一个主要问题是其安全性和有效性难以保证,即不能达到治疗基因表达的空间、时序和表达水平的精确定位,特别是治疗基因表达的选择性不高,在非靶组织/细胞表达易产生毒副作用,并降低疗效。通过组织/细胞特异性转录调控元件使外源基因准确、有效地表达于特定组织细胞,从而提高基因治疗的有效性和安全性,已成为基因治疗领域的研究热点。目前研究表明,肝组织中的白蛋白基因和甲胎蛋白基因里有肝脏特异性转录调控序列如启动子、增强子,能启动基因仅在肝组织表达,故它们在转基因动物和基因治疗中得到广泛应用,且其联合应用对提高肝脏的特异性和转录活性有一定作用,在基因治疗研究中也得到了很好的应用,为病毒性肝炎、遗传代谢疾病、肿瘤性疾病等与肝脏密切相关疾病的致病机制和基因治疗的研究奠定了基础。本文就肝脏特异性转录调控序列的研究进展进行综述。
Gene therapy is a rapidly growing treatment in recent years. Currently, one of the major problems restricting the development of gene therapy is that it is difficult to guarantee its safety and effectiveness, that is, the precise positioning of the space, the timing and the expression level of therapeutic gene expression can not be achieved. In particular, Selective treatment of gene expression is not high, non-target tissue / cell expression prone to toxic side effects, and reduce the efficacy. It has become a research hotspot in the field of gene therapy that the exogenous genes are expressed accurately and efficiently in specific tissue cells through tissue / cell-specific transcriptional regulatory elements to improve the efficiency and safety of gene therapy. Present studies have shown that liver-specific albumin and alpha-fetoprotein genes have liver-specific transcriptional regulatory sequences such as promoters and enhancers, and promotable genes are expressed only in liver tissues, so they are obtained in transgenic animals and gene therapy Widely used, and its combined application to improve liver specificity and transcriptional activity has a role in gene therapy research has also been very good application, for the virus hepatitis, genetic metabolic diseases, neoplastic diseases and other closely related to the liver The pathogenesis of disease and gene therapy laid the foundation for the study. This article reviews the progress of liver-specific transcriptional regulatory sequences.