CRISPR-Cas9 CCR5 Gene Editing for Functional Cure in HIV-Infected Individuals

Mpora Kakwanzi Evelyn

Department of Pharmacognosy Kampala International University Uganda

Email: evelyne.mpora@studwc.kiu.ac.ug

ABSTRACT

HIV persistence within latent reservoirs represents the principal barrier to cure despite lifelong antiretroviral therapy (ART). The CCR5 gene encodes a co-receptor essential for HIV-1 entry into CD4⁺ T cells, and individuals homozygous for the CCR5-Δ32 mutation exhibit natural resistance to infection. This observation has inspired therapeutic strategies to recreate this phenotype through gene editing. This review critically examined the translational and clinical evidence on CRISPR-Cas9-mediated CCR5 disruption as a potential functional cure strategy in HIV-infected individuals. A structured literature search of PubMed, Scopus, and ClinicalTrials.gov (2014–2025) identified peer-reviewed clinical and translational studies investigating CRISPR-Cas9-based CCR5 gene editing in human subjects living with HIV. CRISPR-Cas9 enables precise CCR5 knockout in autologous hematopoietic stem cells (HSCs) and CD4⁺ T cells, generating HIV-resistant progeny following transplantation or adoptive transfer. Early clinical trials demonstrated feasibility, with edited cells persisting and reconstituting immune function without major toxicity. However, editing efficiency, incomplete reservoir clearance, off-target effects, and limited engraftment restrict durable viral remission. Combinatorial approaches integrating latency-reversing agents or dual co-receptor targeting may enhance efficacy. CRISPR-Cas9 CCR5 gene editing offered a rational, biologically grounded path toward a functional HIV cure. Yet, translational success demands improved delivery systems, refined editing fidelity, and synergistic adjunctive strategies. Future human trials must prioritize long-term safety, durable reconstitution of HIV-resistant immunity, and reservoir eradication endpoints.

Keywords: CRISPR-Cas9, CCR5, HIV functional cure, Gene editing, Hematopoietic stem cells

CITE AS: Mpora Kakwanzi Evelyn (2026). CRISPR-Cas9 CCR5 Gene Editing for Functional Cure in HIV-Infected Individuals. IAA  Journal of Applied Sciences 14(1):1-5. https://doi.org/10.59298/IAAJAS/2026/14115