Newer gene editing technologies toward HIV gene therapy.
Newer gene editing technologies toward HIV gene therapy.
复制标题
DOI：
10.3390/v5112748
复制
发表时间：
2013-11-14
期刊：
影响因子：
--
通讯作者：
Shankar P
中科院分区：
文献类型：
--
作者：
Manjunath N;Yi G;Dang Y;Shankar P
尽管高效抗逆转录病毒疗法（HAART）在改善艾滋病毒感染过程中取得了巨大成功，但由于与终身治疗相关的实际问题，人们正在寻求替代治疗方法。接受 CCR5 阴性捐赠者骨髓移植的所谓“柏林患者”体内的艾滋病毒被根除，这重新点燃了人们对基因组工程策略以实现相同效果的兴趣。随着对 DNA 修复机制、DNA 与转录因子的相互作用以及细菌防御机制的了解的最新进展，细胞内精确的基因编辑现在已成为现实。在过去的几年里，出现了四种新技术，它们可以识别特定的 DNA 靶序列，从而实现位点特异性基因编辑：归巢核酸内切酶、ZFN、TALEN 和 CRISPR/Cas9 系统。最新的 CRISPR/Cas9 系统使用与 Cas9 核酸酶结合的一小段互补 RNA 来识别和切割靶 DNA，这与之前的技术不同，之前的技术使用锌指蛋白的 DNA 结合基序或与核酸内切酶融合的转录激活子样效应分子来介导序列特异性 DNA 切割。与 RNA 干扰不同，RNA 干扰需要效应器部分持续存在来维持基因沉默，而新技术可以在单次治疗后永久破坏目标基因。在这里，我们回顾了用于艾滋病毒治疗的新型基因编辑策略的应用、局限性和未来前景。
Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.
登录
查看更多内容
影响因子：
3.7
作者：
Geissler R;Scholze H;Hahn S;Streubel J;Bonas U;Behrens SE;Boch J
通讯作者：
Boch J
影响因子：
17.3
作者：
Gaj, Thomas;Gersbach, Charles A.;Barbas, Carlos F., III
通讯作者：
Barbas, Carlos F., III
影响因子：
12.4
作者：
Alwin, S;Gere, MB;Cathomen, T
通讯作者：
Cathomen, T
影响因子：
46.9
作者：
Cho, Seung Woo;Kim, Sojung;Kim, Jin-Soo
通讯作者：
Kim, Jin-Soo
影响因子：
48
作者：
Gaj, Thomas;Guo, Jing;Kato, Yoshio;Sirk, Shannon J.;Barbas, Carlos F., III
通讯作者：
Barbas, Carlos F., III