KIU Publications

Human immunodeficiency virus infection remains a major global health challenge despite major advances in antiretroviral therapy. Current treatment requires lifelong drug administration and does not eliminate latent viral reservoirs, creating a persistent need for innovative therapeutic strategies capable of achieving durable viral control. Viral entry into CD4-positive T lymphocytes requires interaction between the viral envelope glycoprotein and host cell receptors, including the chemokine receptor CCR5, which served as a principal co-receptor during early infection. The purpose of this review was to evaluate zinc finger nuclease-mediated disruption of the CCR5 gene as a host-directed therapeutic approach for long-term control of HIV infection. A structured narrative review methodology was used to synthesize findings from peer-reviewed studies addressing molecular mechanisms, gene editing efficiency, and therapeutic outcomes of CCR5-targeted zinc finger nuclease strategies. Evidence indicates that zinc finger nuclease-induced CCR5 disruption generated HIV resistant immune cells and can produce sustained persistence of modified lymphocytes in experimental and clinical settings. Gene-edited cells exhibit reduced susceptibility to viral entry and may contribute to partial control of viral replication. Zinc finger nuclease-mediated CCR5 disruption represented a promising host-directed therapeutic strategy with potential to reduce dependence on lifelong antiretroviral therapy. Continued clinical investigation and optimization of gene editing delivery systems were recommended to advance this approach toward durable HIV control.