Refining Anti-HIV Gene Therapies
Researchers use modified stem cells to defend against and attack HIV in a multi-pronged approach
By Jeffrey Laurence, M.D.
Research question
Anti-HIV therapies based on human stem cells genetically engineered to inhibit HIV are promising approaches to both achieving lifelong remission and potentially curing HIV. These self-perpetuating cells could continuously generate immune cells capable of inhibiting HIV spread while being resistant to HIV.
However, the efficiency of such gene modifications, and the extent to which modified cells are maintained in the body, remain sub-optimal. So, how might these gene therapies be improved?
Dr. Anjie Zhen (center) of UCLA, with her team (l-r) Wally Wennerberg, Hwee Ng, Dr. Li Wang, Nicholas Tien, Dr. Caitlin Kan, Dr. Shallu Tomer
Findings
The current investigators developed a multi-pronged genetic approach to targeting HIV. They utilized a modified mouse lentivirus to introduce an inhibitory RNA against the HIV coreceptor CCR5, along with an inhibitor of HIV cell fusion to defend against HIV infection and a CAR strategy—similar to that used to cure several types of human cancers—to attack cells already infected with HIV. They also introduced a “safety switch,” by which genetically engineered cells could be eliminated in the body by administering a specific drug in the unlikely event that unanticipated side effects occurred.
This strategy was tested in mice “humanized” by the introduction of human bone marrow, liver, and thymus gland cells and then infected with HIV.
HIV viral loads were reduced by at least 90%, an effect lasting for six weeks after a single injection of the lentivirus.
Impact
Although the magnitude of the anti-HIV effects achieved in mice was modest, the authors concluded that they “provide valuable insight on the development, protection, and efficacy of engineered T cells from anti-HIV-1 gene-modified human [stem cells]. For clinical application, we recognize that there are still many obstacles to overcome.”
amfAR’s role
amfAR was a funder of this research. amfAR grantee Anjie Zhen, PhD, of the University of California, Los Angeles, was a co-author of the paper.
Original article
https://pubmed.ncbi.nlm.nih.gov/40503012/
Dr. Laurence is amfAR’s senior scientific consultant.
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