Freen-van Heeren Julian J
Independent Researcher, Amsterdam, The Netherlands.
BioTech (Basel). 2022 Jul 14;11(3):25. doi: 10.3390/biotech11030025.
Human immunodeficiency virus (HIV) infection can be controlled by anti-retroviral therapy. Suppressing viral replication relies on life-long medication, but anti-retroviral therapy is not without risks to the patient. Therefore, it is important that permanent cures for HIV infection are developed. Three patients have been described to be completely cured from HIV infection in recent years. In all cases, patients received a hematopoietic stem cell (HSC) transplantation due to a hematological malignancy. The HSCs were sourced from autologous donors that expressed a homozygous mutation in the gene. This mutation results in a non-functional receptor, and confers resistance to CCR5-tropic HIV strains that rely on CCR5 to enter host cells. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) system is one of the methods of choice for gene editing, and the CRISPR/Cas system has been employed to target loci of interest in the context of HIV. Here, the current literature regarding CRISPR-mediated genome editing to render cells resistant to HIV (re)-infection by knocking out the co-receptors CCR5 and CXCR4 is summarized, and an outlook is provided regarding future (research) directions.
人类免疫缺陷病毒（HIV）感染可通过抗逆转录病毒疗法得到控制。抑制病毒复制依赖于终身用药，但抗逆转录病毒疗法对患者并非没有风险。因此，开发针对HIV感染的永久性治愈方法非常重要。近年来，已有三名患者被描述为完全治愈了HIV感染。在所有病例中，患者因血液系统恶性肿瘤接受了造血干细胞（HSC）移植。造血干细胞来自在该基因中表达纯合突变的自体供体。这种突变导致受体无功能，并赋予对依赖CCR5进入宿主细胞的CCR5嗜性HIV毒株的抗性。成簇规律间隔短回文重复序列（CRISPR）/CRISPR相关蛋白（Cas）系统是基因编辑的首选方法之一，并且CRISPR/Cas系统已被用于在HIV背景下靶向感兴趣的基因座。在此，总结了关于通过敲除共受体CCR5和CXCR4使细胞对HIV（再）感染产生抗性的CRISPR介导的基因组编辑的当前文献，并提供了关于未来（研究）方向的展望。
