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[利用逆转录病毒整合酶和转座酶进行定向DNA整合的方法]

[Approaches towards directed DNA integration by the use of retroviral integrases and transposases].

作者信息

Kniazhanskaia E S, Kondrashina O V, Gottikh M B

出版信息

Mol Biol (Mosk). 2011 Nov-Dec;45(6):931-48.

Abstract

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.

摘要

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。

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