CRISPR-Cas9 Gene Editing to Achieve HIV Cure: Current Progress and Barriers
Taliikwa Nicholas Ceaser
Department of Pharmacognosy Kampala International University Uganda
Email:ceaser.taliikwa@studwc.kiu.ac.ug
ABSTRACT
Human immunodeficiency virus type 1 persisted as a global health challenge affecting approximately 39 million individuals worldwide, with current antiretroviral therapy requiring lifelong adherence while failing to eliminate latent viral reservoirs. CRISPR-Cas9 represented a revolutionary gene editing technology capable of precise genomic modifications, offering unprecedented opportunities to disrupt integrated proviral DNA and confer resistance to viral entry through targeted modification of host cellular factors. This review critically examined the application of CRISPR-Cas9 gene editing systems toward achieving functional cure or eradication of human immunodeficiency virus infection, evaluating molecular strategies, preclinical evidence, clinical translation efforts, and obstacles limiting therapeutic implementation. A comprehensive synthesis of mechanistic studies, preclinical models, early phase clinical trials, and theoretical frameworks published through early 2025 addressing CRISPR-Cas9 targeting of integrated provirus, CCR5 coreceptor modification, and combinatorial approaches was utilized in writing this review. CRISPR-Cas9 systems demonstrated capacity to excise integrated proviral sequences from infected cell genomes, disrupt CCR5 coreceptor expression to prevent viral entry, and target conserved viral regulatory elements across diverse human immunodeficiency virus subtypes in cellular and animal models. However, substantial barriers persisted including incomplete elimination of latent reservoirs, off target genomic modifications, inefficient delivery to anatomical sanctuary sites, immune responses against Cas9 protein, viral escape through sequence variation, and technical challenges in achieving therapeutically relevant editing frequencies in vivo. While CRISPR-Cas9 technologies offered compelling theoretical frameworks for human immunodeficiency virus cure, translation from preclinical promise to clinical reality required innovations in delivery systems, editing efficiency, safety profiles, and strategies addressing viral reservoir heterogeneity.
Keywords: CRISPR-Cas9, Human immunodeficiency virus cure, Proviral excision, CCR5 modification, Gene therapy.
CITE AS: Taliikwa Nicholas Ceaser (2026). CRISPR-Cas9 Gene Editing to Achieve HIV Cure: Current Progress and Barriers. IAA Journal of Scientific Research 13(1):12-17.