Cell and Gene Technology Group, Institute of Gene Biology of Russian Academy of Science, Moscow, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology of Russian Academy of Science, Moscow, Russia.
Front Cell Infect Microbiol. 2022 May 25;12:880030. doi: 10.3389/fcimb.2022.880030. eCollection 2022.
Although highly active antiretroviral therapy (HAART) can robustly control human immunodeficiency virus (HIV) infection, the existence of latent HIV in a form of proviral DNA integrated into the host genome makes the virus insensitive to HAART. This requires patients to adhere to HAART for a lifetime, often leading to drug toxicity or viral resistance to therapy. Current genome-editing technologies offer different strategies to reduce the latent HIV reservoir in the body. In this review, we systematize the research on CRISPR/Cas-based anti-HIV therapeutic methods, discuss problems related to viral escape and gene editing, and try to focus on the technologies that effectively and precisely introduce genetic modifications and confer strong resistance to HIV infection. Particularly, knock-in (KI) approaches, such as mature B cells engineered to produce broadly neutralizing antibodies, T cells expressing fusion inhibitory peptides in the context of inactivated viral coreceptors, or provirus excision using base editors, look very promising. Current and future advancements in the precision of CRISPR/Cas editing and its delivery will help extend its applicability to clinical HIV therapy.
尽管高效抗逆转录病毒疗法（HAART）可以有效地控制人类免疫缺陷病毒（HIV）感染，但 HIV 以整合到宿主基因组中的前病毒 DNA 的形式存在潜伏，使病毒对 HAART 不敏感。这要求患者终生坚持 HAART，常常导致药物毒性或病毒对治疗产生耐药性。目前的基因组编辑技术提供了不同的策略来减少体内潜伏的 HIV 储库。在这篇综述中，我们系统地研究了基于 CRISPR/Cas 的抗 HIV 治疗方法，讨论了与病毒逃逸和基因编辑相关的问题，并试图关注那些能够有效且精确地引入遗传修饰并赋予 HIV 感染强抗性的技术。特别地，敲入（KI）方法，如经过工程改造以产生广泛中和抗体的成熟 B 细胞、在失活的病毒核心受体背景下表达融合抑制肽的 T 细胞，或使用碱基编辑器进行前病毒切除，看起来非常有前景。CRISPR/Cas 编辑及其递呈的精准度的当前和未来进展将有助于将其应用扩展到临床 HIV 治疗中。
