CRISPR-Cas Gene Editing Strategies for HIV Reservoir Eradication and Functional Cure

Namirimu Sandrah

Department of Pharmacology and Toxicology Kampala International University Uganda

Email: sandrahnamirimu@studwc.kiu.ac.ug

ABSTRACT

Human immunodeficiency virus (HIV) persists in latent reservoirs despite effective antiretroviral therapy, presenting a fundamental barrier to achieving a functional cure. The emergence of clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems had revolutionized gene editing approaches for HIV eradication strategies. This review examined the current state of CRISPR-Cas technologies targeting HIV reservoirs, evaluating molecular mechanisms, therapeutic efficacy, and clinical translation potential. A comprehensive literature search was conducted using PubMed, Web of Science, and Embase databases from 2012-2025, focusing on peer-reviewed studies examining CRISPR applications in HIV reservoir targeting, latency reversal, and functional cure strategies. Current CRISPR-Cas approaches demonstrated promising results in disrupting HIV proviral DNA, with Cas9-mediated excision achieving up to 95% reduction in integrated viral sequences in vitro. Multiplex targeting strategies combining CCR5 knockout with proviral excision showed enhanced therapeutic potential. Base editing and prime editing technologies offered improved precision for HIV genome modification with reduced off-target effects. Clinical translation faced challenges including delivery efficiency, off-target mutagenesis, and reservoir heterogeneity. CRISPR-Cas systems represent a transformative approach toward HIV functional cure, with ongoing clinical trials demonstrating feasibility and preliminary safety profiles. Combination strategies integrating CRISPR with latency-reversing agents and immunotherapy hold significant promise for comprehensive reservoir eradication.

Keywords: CRISPR-Cas, HIV reservoir, Gene editing, Functional cure, Proviral excision.

CITE AS: Namirimu Sandrah (2025). CRISPR-Cas Gene Editing Strategies for HIV Reservoir Eradication and Functional Cure. IDOSR JOURNAL OF APPLIED SCIENCES 10(2):64-68, 2025. https://doi.org/10.59298/IDOSRJAS/2025/102.6468