Kniazhanskaia E S, Kondrashina O V, Gottikh M B
Mol Biol (Mosk). 2011 Nov-Dec;45(6):931-48.
The ability of retroviruses and transposases to insert own genome into a host-cell allow us to consider them as a preferable object for constructing gene therapy vectors. However, enzymes that perform the insertion of the genetic material do not display a selectivity towards target nucleotide sequences that results in an almost random DNA introduction into the recipient cell genome. Random insertion leads to mutations which might cause a number of undesirable consequences including neoplastic transformation in the cell. Thereby, in order to achieve a successful functioning of retroviral and trasposonal genetic therapy systems, it is essential to modify them in such a way that directed integration of the vector in a target sequence in the human genome could be achieved. In the review approaches that have been developed for a high specific modification of genome, including the construction of hybrid proteins on the basis of retroviral integrases, transposases, as well as cellular factors interacting with these enzymes, are presented.
逆转录病毒和转座酶将自身基因组插入宿主细胞的能力,使我们将它们视为构建基因治疗载体的优选对象。然而,执行遗传物质插入的酶对目标核苷酸序列不具有选择性,这导致几乎随机地将DNA引入受体细胞基因组。随机插入会导致突变,这可能会引发许多不良后果,包括细胞的肿瘤转化。因此,为了使逆转录病毒和转座子基因治疗系统成功发挥作用,必须对它们进行改造,以便能够实现载体在人类基因组目标序列中的定向整合。本文综述了为实现基因组的高特异性修饰而开发的方法,包括基于逆转录病毒整合酶、转座酶以及与这些酶相互作用的细胞因子构建杂交蛋白。