Innovative mRNA Nanoparticles Reactivate Dormant HIV in White Blood Cells

A groundbreaking study published in Nature Communications explores a novel approach to tackling hidden HIV reservoirs within the body. Researchers have developed potent mRNA-lipid nanoparticles (LNPs), similar to those used in COVID-19 vaccines and emerging gene therapies, to target dormant HIV infected white blood cells, specifically resting CD4+ T cells.

HIV has long posed a challenge to cure because it can hide in a latent state inside resting immune cells, evading the immune system and existing treatments. This reservoir of latent HIV can reactivate and restart infection even after years of antiretroviral therapy (ART), which suppresses the virus but does not eliminate these hiding cells.

The newly developed LNP system delivers messenger RNA (mRNA) into these hard-to-target cells, prompting the cells to produce proteins that activate HIV’s genes. By doing so, the virus is 'flushed out' of hiding, making infected cells detectable and accessible for immune clearance or targeted destruction. The approach leverages the same technology behind common COVID-19 vaccines, ensuring high efficiency and safety.

This targeted method achieved over 75% transfection efficiency in ex vivo CD4+ T cells from patients with HIV, without causing toxicity or abnormal immune activation. The researchers encoded a portion of the HIV Tat protein, which plays a critical role in initiating viral gene expression, thereby reversing latency.

Furthermore, the LNP system successfully delivered CRISPR activation tools to manipulate specific genes related to HIV and host responses, highlighting its potential in advanced immunotherapies. Although promising, further studies are planned to determine the optimal therapeutic dose, biodistribution, and safety profile before clinical application.

This innovative approach could mark a significant step toward HIV eradication by precisely targeting and eliminating the viral reservoirs that sustain infection, bringing us closer to the goal of a functional cure.