Various antiretroviral drugs do not kill or cure the human immunodeficiency virus (HIV) but do prevent the replication of the virus. The combination of antiretroviral drugs is known as highly active antiretroviral therapy (HAART). Current drug therapies effectively suppress HIV-1 replication but do not inactivate the provirus that persists in latent reservoirs. Guide RNA (gRNA)-directed CRISPR/Cas9 system can be used for sequence-specific attacks on this proviral DNA. The biggest achievement might be the complete elimination of HIV from infected cells. A study revealed that the tail injection, in transgenic mice and rats having HIV-1 genome, of an adenoassociated virus (AAV) vector expressing a short version of the Cas9 endonuclease (saCas9) and the gRNAs resulted in the cleavage of integrated HIV-1 DNA and excision of a DNA fragment spanning between the LTR and Gag gene in the spleen, liver, heart, kidney, and circulating lymphocytes. HIV-1 has capacity to escape the attack on its genome from most of inhibitors. Thus, to achieve successful antiretroviral treatment, combinations of several antiviral therapies have been applied that are based on two important facts. The first is that multiple drugs lead to synergistic or additive inhibition, and the second is that the combinational therapy increases chances of drug resistance. The success that has been achieved with the help of the genetically engineered tool CRISPR is that dCas9 protein alone can efficiently silence viral gene expression in bacteria with sgRNA. All the reported investigations have indicated that CRISPR/Cas9 can be used as immune machinery into human cells in the form of novel antivirus tools.

中文翻译：

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CRISPR-CAS 替代 HIV 抗病毒药物：最新进展。


各种抗逆转录病毒药物不能杀死或治愈人类免疫缺陷病毒（HIV），但可以防止病毒复制。抗逆转录病毒药物的组合被称为高效抗逆转录病毒疗法（HAART）。目前的药物疗法可有效抑制 HIV-1 复制，但无法灭活潜伏病毒库中持续存在的原病毒。引导 RNA (gRNA) 引导的 CRISPR/Cas9 系统可用于对该原病毒 DNA 进行序列特异性攻击。最大的成就可能是从受感染的细胞中完全消除艾滋病毒。一项研究表明，在具有 HIV-1 基因组的转基因小鼠和大鼠中，尾部注射表达短版 Cas9 核酸内切酶 (saCas9) 和 gRNA 的腺相关病毒 (AAV) 载体，导致整合的 HIV-1 裂解DNA 和跨越脾、肝、心、肾和循环淋巴细胞中 LTR 和 Gag 基因之间的 DNA 片段的切除。 HIV-1有能力逃避大多数抑制剂对其基因组的攻击。因此，为了实现成功的抗逆转录病毒治疗，基于两个重要事实，已经应用了几种抗病毒疗法的组合。第一个是多种药物导致协同或相加抑制，第二个是联合治疗增加了耐药性的机会。借助基因工程工具 CRISPR 所取得的成功是，仅 dCas9 蛋白就可以通过 sgRNA 有效沉默细菌中的病毒基因表达。所有报道的研究都表明 CRISPR/Cas9 可以以新型抗病毒工具的形式用作人体细胞的免疫机制。