PERSPECTIVE article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1590690
CCR5 Gene Editing and HIV Immunotherapy: Current Understandings, Challenges, and Future Directions
Provisionally accepted
- Department of Orthopedics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Human immunodeficiency virus (HIV) infection remains a major global public health challenge. Although highly active antiretroviral therapy (HAART or ART) can effectively control viral replication, it fails to eradicate latent viral reservoirs and poses limitations such as lifelong medication and cumulative drug toxicity. This study focuses on the pivotal role of C-C chemokine receptor 5 (CCR5) gene editing in HIV immunotherapy, particularly highlighting the natural resistance to R5-tropic HIV strains observed in the "Berlin" and "London" patients carrying the homozygous CCR5-Δ32 mutation. We further explore the synergistic potential of multiplex gene editing strategies-including CCR5, CXCR4, and HIV LTR loci-and the combinatorial mechanisms between gene editing technologies and immunotherapy. A personalized treatment framework is proposed to address the clinical heterogeneity among people living with HIV. In addition, we assess the balance between long-term safety and global accessibility of gene-editing approaches such as CRISPR/Cas9, emphasizing strategies to enhance therapeutic efficacy while reducing cost and off-target effects. Our findings suggest that the integration of CCR5-targeted gene editing with immune-based interventions holds great promise for overcoming current therapeutic limitations and achieving functional HIV cure. However, key challenges-such as immune rejection, viral tropism switching, and economic feasibility-must be resolved. This integrative approach provides a robust theoretical and technical foundation for the next generation of HIV treatment paradigms.
Keywords: HIV, CCR5, gene editing, Immunotherapy, Synergistic strategy, viral reservoir, Challenges, Future Directions
Received: 10 Mar 2025; Accepted: 02 Jun 2025.
Copyright: © 2025 Wang, Liu and Xun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jian-Jun Xun, Department of Orthopedics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.