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Nanoparticles and CRISPR: A Dynamic Duo in the Treatment of HIV-1?

July 19, 2019

In 2017, approximately 36.9 million people were living with human immunodeficiency virus type 1 (HIV-1). Antiretroviral therapy (ART) is the current standard of care for these patients; however, treatment effectiveness is limited by the inability to remove viral DNA once integrated into the host genome. New research suggests this barrier to treatment may have met its match…

 

Researchers at the University of Nebraska have pioneered a novel therapeutic strategy branded “LASER ART” (long-acting slow-effective release ART). This technology works by delivering a concentrated stream of nanoparticles filled with antiretroviral prodrugs to patients’ viral reservoirs by intramuscular injection. This approach maximizes uptake of antiretroviral agents by macrophages, minimizes off-target effects and reduces the dosing frequency from daily to weekly. The researchers took this one step further and followed LASER ART with intravenously administered clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 to mediate excision of the viral gag gene from host genomes. LASER ART and CRISPR-Cas9 are thought to work synergistically; CRISPR-Cas9’s ability to target and excise integrated viral DNA is increased due to LASER ART’s ability to suppress viral replication.

 

LASER ART followed by treatment with CRISPR-Cas9 three weeks later has shown promise in

HIV-1-infected mouse models. DNA and RNA analyses were performed on 7 mice at 5 weeks following the procedure. This treatment approach completely eliminated viral nucleic acids in the tissues and plasma of two subjects and showed an impressive decline in viral load in the remaining subjects. What’s more, bioinformatic analyses of treated mice suggested no off-target effects could be attributed to CRISPR-Cas9. The team is anticipating proceeding to trials in nonhuman primates in the upcoming year. We are excited to learn how this treatment strategy will fare in future studies and if it will be able to offer patients with HIV-1 a new treatment option!

 

 

 

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