CRISPR-Cas9 Mediated Genome Editing a Promise to Cure HIV: A Systematic Review
DOI:
https://doi.org/10.23918/eajse.v11i3p14Keywords:
CRISPR-Cas9, HIV, CCR5, CXCR4, Genome EditingAbstract
Human Immunodeficiency Virus (HIV-1) infection might be controlled using long-term antiretroviral therapy. However, it causes various side effects rather than its cost-effectiveness. Thus, the development of a permanent cure for HIV-1 that most probably relies on gene therapy is highly required. Relying on that, genome editing approaches like Clustered Regularly Interspaced Short Palindromic Repeats associated with Cas9 (CRISPR-Cas9) have been utilized to target coreceptors, including CCR5 and CXCR4, hoping to find a curative method against HIV infection. Accordingly, the current study aims to systematically review CRISPR-Cas9 mediating genome editing studies, mainly CCR5 or CXCR4 or simultaneous genome editing to make HIV resistant primary human CD4+ T cells. A systematic review was conducted on original articles focusing on CRISPR-Cas9 mediated genome editing in HIV, published between 2015 and 2023. As a result, the CRISPR-Cas9 technology has demonstrated effective gene editing to confer HIV-1 resistance by targeting CCR5 and CXCR4 receptors in CD4+ T cells. Studies show that knockout of CCR5 or CXCR4, through CRISPR-Cas9 mediated frameshift insertions, base editing, and other genetic interventions, provides substantial resistance to HIV-1, with no major cytotoxic effects observed in primary T cells. Dual knockout of CXCR4 and CCR5 offers resistance to both X4- and R5-tropic HIV strains, suggesting enhanced protective potential. However, challenges remain, particularly due to CXCR4's crucial cellular roles, necessitating careful assessment of functional impacts and off-target effects. Additionally, leveraging natural mutations like CCR5∆32 has inspired promising avenues for durable HIV-1 resistance. While targeting viral genomes, especially latent reservoirs, appears safer by avoiding host genome alterations, reinfection risks persist. These findings highlight the promise of CRISPR-based HIV therapies, though clinical translation will require rigorous optimization and evaluation.
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