CRISPR-Cas9 Gene Editing Permanently Eliminates HIV-1 DNA

Alex, R. Gonçalves
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Abstract

Submit Manuscript | http://medcraveonline.com condition as a situation where the host’s genome was invaded, manipulated and exploited by a viral intruder. By the end of 2016, there were 36.9 million HIV-infected individuals living around the world and 19.5 million people were accessing antiretroviral therapy (UNAIDS 2017). We can typically treat patients with antiretroviral therapies and other symptomatic treatments or we can develop new ways to prevent the HIV infection with the development of new vaccines. However, while different vaccines are being tested with various degrees of success, there is still no evidence vaccination will be the best choice due to the HIV infection strategy. Therefore, while scientists keep testing and designing new vaccines against HIV/AIDS, recent advances in personalized medicine can be a game changer. Scientists are evaluating a new CRISPR-Cas9 strategy to achieve a permanent cure for HIV infection. There have been different approaches to treat HIV/ AIDS but there are several reasons preventing scientists from finding a viable cure for the HIV infection, for example, the HIV virus plasticity and its ability to remain in a latent state in hidden HIV reservoirs away from the host immune defense system [1]. A hallmark of the AIDS pathogenesis is the progressive depletion of CD4+ T-cell populations in association with an impaired immunity response [2]. It is that immune response weakening and the inability to initiate an effective cellular immune response against HIV that increases the susceptibility to opportunistic and often deadly infections. An updated list of opportunistic diseases and recommended responses is prepared yearly by the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America [3]. Recent studies identified a new CD4 T-cell HIV reservoir marker that might pave the way for the development of new HIV treatments [4, 5]. CD32a+ lymphocytes can be used to identify the elusive HIV-1 reservoir. That finding may lead to novel insights that will allow the specific targeting and elimination of this resistant HIV reservoir. Establishing CD32a+ as a marker to identify those quiescent HIV cells is the perfect target to unleash the most recent genetic engineering tool that allows the modification of the hosts’ genome, the CRISPR-Cas9 method. The CRISPR-Cas9 gene editing complex is an elegant tool from the Streptococcus pyogenes [6]. The Cas9 nuclease protein uses a guide RNA sequence to cut DNA at a complementary site making this process the ideal mechanism to direct a precise genetic deletion and modification of the genome.
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CRISPR-Cas9基因编辑永久消除HIV-1 DNA
提交手稿|http://medcraveonline.com宿主基因组被病毒入侵者入侵、操纵和利用的情况。截至2016年底,世界各地有3690万艾滋病毒感染者,1950万人正在接受抗逆转录病毒治疗(联合国艾滋病规划署,2017年)。我们通常可以用抗逆转录病毒疗法和其他症状治疗来治疗患者,或者我们可以通过开发新疫苗来开发预防艾滋病毒感染的新方法。然而,尽管不同的疫苗正在测试中,并取得了不同程度的成功,但由于艾滋病毒感染策略,仍然没有证据表明接种疫苗将是最佳选择。因此,当科学家们不断测试和设计新的艾滋病毒/艾滋病疫苗时,个性化医学的最新进展可能会改变游戏规则。科学家们正在评估一种新的CRISPR-Cas9策略,以实现HIV感染的永久治愈。治疗HIV/AIDS有不同的方法,但有几个原因阻碍了科学家找到治疗HIV感染的可行方法,例如,HIV病毒的可塑性及其在远离宿主免疫防御系统的隐藏HIV库中保持潜伏状态的能力[1]。艾滋病发病机制的一个标志是CD4+T细胞群的逐渐耗竭与免疫反应受损有关[2]。正是这种免疫反应减弱,无法启动针对艾滋病毒的有效细胞免疫反应,增加了对机会性感染的易感性,而且往往是致命的感染。美国疾病控制与预防中心、美国国立卫生研究院和美国传染病学会HIV医学协会每年都会编制一份最新的机会性疾病和建议应对措施清单[3]。最近的研究发现了一种新的CD4 T细胞HIV库标志物,可能为开发新的HIV治疗方法铺平道路[4,5]。CD32a+淋巴细胞可用于鉴定难以捉摸的HIV-1库。这一发现可能会带来新的见解,从而能够特异性地靶向和消除这种具有耐药性的艾滋病毒库。建立CD32a+作为识别那些静止的HIV细胞的标记物,是释放最新的基因工程工具CRISPR-Cas9方法的完美靶点,该工具可以修饰宿主的基因组。CRISPR-Cas9基因编辑复合体是化脓性链球菌的一种优雅工具[6]。Cas9核酸酶蛋白使用引导RNA序列在互补位点切割DNA,使这一过程成为指导基因组精确遗传缺失和修饰的理想机制。
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