The Role of CRISPR-Cas۹ in Functional Cure for HIV Virus: A Systematic Review

Introduction: The CRISPR-Cas۹ gene-editing system presents a transformative approach to HIV treatment. By modifying host genes (e.g. CCR۵A۳۲) and targeting viral genomic sequences, it prevents viral entry and replication. However, clinical translation faces challenges including off-target effects and delivery limitations. Through enhanced specificity and integration with existing therapies, CRISPR-based strategies could revolutionize HIV cure research, offering new possibilities for durable viral suppression and reservoir elimination. Method: A systematic review was conducted from ۲۰۲۳ to ۲۰۲۵ using PubMed, Web of Science and Scopus databases, using the keywords 'CRISPR-Cas۹', 'HIV Virus' and 'Therapeutic'. The CASP checklist was used for qualitative assessment. Discussion: The CRISPR-Cas۹ system blocks HIV-۱ entry into immune cells by introducing protective mutations (e.g. CCR۵A۳۲) in hematopoietic stem cells, and by combining techniques such as fusion inhibitors (e.g. C۴۶) or simultaneous interconnection of CCR۵/CXCR۴ co-receptors, it establishes broad resistance to various viral strains. This technology also targets directly critical regions of the viral genome (e.g. LTR) through certain gRNAs, inactivates or excretes the provirus, and is used in combinatorial strategies shock and kill to eliminate latent reservoirs. However, challenges such as off-target activity, reduced transplantation of edited cells (especially after a CXCR۴ damage), viral escape mutations, and limitations in the efficient delivery of the system in target cells have hampered widespread clinical application. To realize the potential of a definitive HIV treatment, it is essential to optimize the technology (for example, the design of more accurate gRNAs, the development of caustic variants), integrate with existing treatments (such as ART) and to do long-term assessment in pre-clinical models. Despite these obstacles, CRISPR-Cas۹ has become a paradigm changing AIDS gene therapy, opening up new horizons for personalized treatment methods. Conclusion: CRISPR-Cas۹ gene editing offers a transformative strategy for HIV treatment by simultaneously targeting host genes and viral DNA. Preclinical studies confirm its ability to inhibit viral entry and reactivate latent reservoirs. However, challenges such as off target effects, delivery limitations, and viral escape mutations remain critical hurdles. Combining CRISPR with antiretroviral therapy and latency reversing agents could enhance its efficacy. Future research must focus on improving specificity,

کلیدواژه ها:

CRISPR-Cas۹ ، HIV Virus ، Therapeutic