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基于基因编辑的新型艾滋病疗法。

Novel AIDS therapies based on gene editing.

作者信息

Khalili Kamel, White Martyn K, Jacobson Jeffrey M

机构信息

Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA.

Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA.

出版信息

Cell Mol Life Sci. 2017 Jul;74(13):2439-2450. doi: 10.1007/s00018-017-2479-z. Epub 2017 Feb 16.

Abstract

HIV/AIDS remains a major public health issue. In 2014, it was estimated that 36.9 million people are living with HIV worldwide, including 2.6 million children. Since the advent of combination antiretroviral therapy (cART), in the 1990s, treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS has become increasingly rare. However, while people with HIV can expect to live a normal life span with cART, lifelong medication is required and cardiovascular, renal, liver, and neurologic diseases are still possible, which continues to prompt research for a cure for HIV. Infected reservoir cells, such as CD4+ T cells and myeloid cells, allow persistence of HIV as an integrated DNA provirus and serve as a potential source for the re-emergence of virus. Attempts to eradicate HIV from these cells have focused mainly on the so-called "shock and kill" approach, where cellular reactivation is induced so as to trigger the purging of virus-producing cells by cytolysis or immune attack. This approach has several limitations and its usefulness in clinical applications remains to be assessed. Recent advances in gene-editing technology have allowed the use of this approach for inactivating integrated proviral DNA in the genome of latently infected cells or knocking out HIV receptors. Here, we review this strategy and its potential to eliminate the latent HIV reservoir resulting in a sterile cure of AIDS.

摘要

艾滋病毒/艾滋病仍然是一个重大的公共卫生问题。2014年,据估计全球有3690万人感染艾滋病毒,其中包括260万儿童。自20世纪90年代联合抗逆转录病毒疗法(cART)问世以来,治疗取得了巨大成功,在世界许多地区,艾滋病毒已成为一种慢性病,发展成艾滋病的情况越来越罕见。然而,虽然感染艾滋病毒的人通过cART有望正常寿命,但需要终身服药,心血管、肾脏、肝脏和神经系统疾病仍有可能发生,这继续促使人们寻找治愈艾滋病毒的方法。受感染的储存细胞,如CD4 + T细胞和髓样细胞,使艾滋病毒以整合的DNA原病毒形式持续存在,并成为病毒重新出现的潜在来源。从这些细胞中根除艾滋病毒的尝试主要集中在所谓的“激活并清除”方法上,即诱导细胞重新激活,从而通过细胞溶解或免疫攻击来清除产生病毒的细胞。这种方法有几个局限性,其在临床应用中的有效性仍有待评估。基因编辑技术的最新进展使得可以使用这种方法来灭活潜伏感染细胞基因组中的整合原病毒DNA或敲除艾滋病毒受体。在此,我们综述了这一策略及其消除潜伏艾滋病毒储存库从而实现艾滋病彻底治愈的潜力。

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