Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Int J Mol Sci. 2023 Jan 13;24(2):1563. doi: 10.3390/ijms24021563.
Human immunodeficiency virus (HIV) infections and HIV-induced acquired immunodeficiency syndrome (AIDS) continue to represent a global health burden. There is currently no effective vaccine, nor any cure, for HIV infections; existing antiretroviral therapy can suppress viral replication, but only as long as antiviral drugs are taken. HIV infects cells of the host immune system, and it can establish a long-lived viral reservoir, which can be targeted and edited through gene therapy. Gene editing platforms based on the clustered regularly interspaced palindromic repeat-Cas system (CRISPR-Cas) have been recognized as promising tools in the development of gene therapies for HIV infections. In this review, we evaluate the current landscape of CRISPR-Cas-based therapies against HIV, with an emphasis on the infection biology of the virus as well as the activity of host restriction factors. We discuss the potential of a combined CRISPR-Cas approach that targets host and viral genes to activate antiviral host factors and inhibit viral replication simultaneously. Lastly, we focus on the challenges and potential solutions of CRISPR-Cas gene editing approaches in achieving an HIV cure.
人类免疫缺陷病毒(HIV)感染和 HIV 引起的获得性免疫缺陷综合征(AIDS)仍然是全球健康的负担。目前,HIV 感染既没有有效的疫苗,也没有治愈方法;现有的抗逆转录病毒疗法可以抑制病毒复制,但只要停止使用抗病毒药物,病毒就会再次复制。HIV 感染宿主免疫系统的细胞,它可以建立一个长期存在的病毒储存库,通过基因治疗可以靶向和编辑这个病毒储存库。基于成簇规律间隔短回文重复-Cas 系统(CRISPR-Cas)的基因编辑平台已被认为是 HIV 感染基因治疗发展的有前途的工具。在这篇综述中,我们评估了基于 CRISPR-Cas 的抗 HIV 疗法的现状,重点关注病毒的感染生物学以及宿主限制因子的活性。我们讨论了靶向宿主和病毒基因的联合 CRISPR-Cas 方法的潜力,这种方法可以同时激活抗病毒宿主因子和抑制病毒复制。最后,我们关注 CRISPR-Cas 基因编辑方法在实现 HIV 治愈方面的挑战和潜在解决方案。