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Novel Delivery System Suppresses HIV in Mice

HIV, the virus that causes AIDS, is one of the world’s most serious public health challenges. Despite advances in our scientific understanding of HIV and its prevention and treatment, there are many who still do not have access to prevention, care, and treatment, and there is still no cure. A new mouse study by researchers at City of Hope and Menzies Health Institute Queensland at Griffith University may provide hope. The researchers report they have developed an anti-HIV protein that suppressed HIV levels in the bone marrow, spleen, and brain of mice and prevented replication.

Their findings are published in Nature Communications in a paper titled, “Exosome-mediated stable epigenetic repression of HIV-1.”

“Human Immunodeficiency Virus (HIV-1) produces a persistent latent infection,” the researchers wrote. “Control of HIV-1 using combination antiretroviral therapy (cART) comes at the cost of life-shortening side effects and development of drug-resistant HIV-1. An ideal and safer therapy should be deliverable in vivo and target the stable epigenetic repression of the virus, inducing a stable ‘block and lock’ of virus expression. Towards this goal, we developed an HIV-1 promoter-targeting Zinc Finger Protein (ZFP-362) fused to active domains of DNA methyltransferase 3 A to induce long-term stable epigenetic repression of HIV-1.”

Their delivery system may pave the way for future therapies that suppress infectious diseases.

“This innovative technology could become a viable way to deliver therapies not only for HIV but also for other diseases, including ones that affect the brain, such as Alzheimer’s and Parkinson’s,” explained Kevin Morris, PhD, senior author of the study and professor from City of Hope’s Center for Gene Therapy and Griffith University’s School of Pharmacy and Medical Sciences.

“The ZPAMt HIV protein repressor we developed is packaged into exosome nanoparticles and can enter cells where it epigenetically silences HIV,” Morris said. “We show that these nanoparticles can systemically ‘block and lock’ HIV expression. This is the first time that block and lock has been successfully delivered to treat HIV in vivo in the brain.”

This finding is both imperative and innovative for diseases such as HIV due to its ability to hide in the brain, making it difficult to treat because of the blood-brain barrier.

“The anti-HIV-1 therapeutic exosomes presented in this study, with additional preclinical safety studies, have the potential to be adopted for clinical trials along with cART for people living with HIV-1, which may reduce the stringency of drug regimen and enhance their quality of life,” concluded the researchers. “Furthermore, we have shown a viable route to achieve specific hypermethylation of an integrated provirus, which can be extended beyond HIV-1/AIDS therapy.”

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