C46 Boosts CRISPR-Based HIV Resistance

The study deployed the CRISPR-Cas9 system to knock out the CCR5 gene in MT4CCR5 cells, a cell line modified to express the CCR5 co-receptor. Concurrently, cells were engineered to express C46, which inhibits the fusion of HIV-1 to host cells, thereby blocking the virus's entry.

The approach led to enhanced protective effects against both R5-tropic and X4-tropic HIV-1, the two main strains responsible for infection. The integration of C46 was confirmed by real-time PCR, and its presence significantly reduced HIV-1 replication in these cells.

Key findings indicate that the combined therapy not only retains but amplifies the efficacy of each component. The CRISPR-mediated CCR5 knockout contributed to a robust resistance against R5-tropic HIV-1. Meanwhile, the addition of C46 provided a strong defence against the X4-tropic strain, showcasing a broad-spectrum resistance capability.

This method proved more effective than using either strategy alone, particularly in preventing high-level HIV-1 infections that are typically challenging to control with single-agent therapies.

The study, led by Suradej Hongeng from Mahidol University in Bangkok, Thailand, was published yesterday in Scientific Reports.