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Cell membrane anchoring strategies for HIV gene therapy

Cellular & Molecular Immunology volume 20, pages 683–685 (2023)Cite this article

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HIV has been a global public health concern since it was discovered in 1981. The development of effective anti-HIV therapy is a top priority, especially as there is no vaccine available. HIV can integrate into the human genome to form a persistent HIV reservoir that cannot be eradicated by current approaches. Although implementation of highly active antiretroviral therapy (HAART), the so-called “cocktail” therapy, has rendered HIV/AIDS a manageable chronic disease, HAART is lifelong treatment and is associated with drug resistance, toxic damage to vital organs, and high costs. Once HAART is stopped, HIV rebound occurs from the reservoir in the host. Although little is known about the biology of HIV reservoirs, there have been an increasing number of cured or near-cured patients in recent years, especially with regard to posttreatment interruption without a viral rebound for a long time, which is called posttreatment control (PTC) or functional cure. Thus, a functional HIV cure has become the mainstay of current treatment approaches.

“Berlin patient”, “London patient” and “Düsseldorf patient” indicate the importance of CCR5∆32 for HIV remission and that infusion of HIV-resistant cells would be a viable treatment strategy for effecting an HIV cure. Nevertheless, due to the difficulty in finding donors with CCR5∆32 mutation, the risk of surgery, and the fact that CCR5∆32 HSCT does not always cure HIV, this HSCT approach is aimed at a very limited population. For safety reasons, membrane-anchored HIV entry inhibitors, such as broadly neutralizing antibodies (bNAbs) and membrane fusion inhibitor peptides, have significant advantages in generating HIV-resistant cells because they block the first step of viral infection, i.e., cell entry.

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Acknowledgements

This work was supported in part by research grants from the National Natural Science Foundation of China (No. 82230076) and the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-037).

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Authors and Affiliations

  1. NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China

    Yani Gong & Yuxian He

  2. Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China

    Yani Gong & Yuxian He

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  1. Yani Gong
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YG and YH drafted and edited the manuscript. YH performed the final proofreading of the manuscript.

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Correspondence to Yuxian He.

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The authors declare no competing interests.

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Gong, Y., He, Y. Cell membrane anchoring strategies for HIV gene therapy. Cell Mol Immunol 20, 683–685 (2023). https://doi.org/10.1038/s41423-023-01006-z

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