GENE EDITING USING CRISPR -CAS9 IN THE FIGHT AGAINST HIV: A LITERATURE REVIEW ON THERAPEUTIC ADVANCES AND LIMITATIONS

Resumo

Human immunodeficiency virus (HIV) remains a major global health challenge due to its ability to establish latent reservoirs and promote chronic immunosuppression, even in the context of advances in antiretroviral therapies, whic h are unable to completely eradicate the virus from the body. In this context, the gene -editing technology CRISPR -Cas9 emerges as an innovative tool with high therapeutic potential, enabling precise and targeted genomic modifications. This study consists of a literature review aiming to analyze current scientific evidence published between 2021 and 2025 regarding the application of CRISPR-Cas9 in HIV treatment, addressing its mechanisms of action, therapeutic strategies, limitations, and future perspectives . This is a descriptive and exploratory review conducted through the analysis of scientific articles indexed in databases such as PubMed, ScienceDirect, and the National Library of Medicine, prioritizing experimental, preclinical, and systematic review stu dies. Study selection considered criteria such as recency, scientific relevance, and therapeutic applicability, allowing a critical and integrated analysis of the main approaches described in the literature. Among the most promising strategies are the dire ct excision of proviral DNA integrated into the host genome, the editing of the CCR5 co -receptor to prevent viral entry, and the “shock and kill” approach, aimed at reactivating and subsequently eliminating latent viral reservoirs. The analyzed results ind icate that CRISPR-Cas9 demonstrates a strong ability to reduce viral reservoirs, interrupt viral replication, and confer resistance to infection in genetically modified cells, with consistent evidence in in vitro and in vivo models. However, significant ch allenges still limit its clinical application, including off -target effects, toxicity associated with double -strand breaks, undesirable immune responses, and limitations in gene repair mechanisms, particularly in homology-directed repair pathways. Recent advances, such as the development of high-fidelity Cas9 variants, base editors, prime editing technologies, and the use of other nucleases such as Cas12 and Cas13, show significant potential to overcome these limitations. In conclusion, CRISPR- Cas9 represents a promising platform for the development of innovative and potentially curative therapies for HIV, although further studies are required to ensure its safety and clinical applicability, reinforcing its role in precision medicine.