Gene Editing System Could Eradicate HIV

Guide RNA shows promise eliminating HIV from the DNA of CD4 T cells.

A specialized gene editing system was able to safely and effectively eliminate HIV-1 from human T cells in a recent study.

HIV/AIDS has killed more than 25 million people since its discovery, and researchers have been working tirelessly to find a cure.

“Antiretroviral drugs are very good at controlling HIV infection,” said senior study investigator Kamel Khalili, PhD. “But patients on antiretroviral therapy who stop taking the drugs suffer a rapid rebound in HIV replication.”

Multiple copies of HIV weakens the immune system and leads to the development of AIDS.

Recent studies have tried to intentionally reactivate HIV in order to stimulate a robust immune response capable of eradicating the virus from infected cells. However, eliminating the virus after it integrated into CD4+ T cells is challenging and recent attempts have been unsuccessful.

A study published in Scientific Reports used a uniquely tailored gene editing technology that specifically targeted HIV-1 proviral DNA.

This approach uses a guide RNA that locates HIV-1 DNA in the T cell genome and the nuclease enzyme that cuts of strands of T cell DNA. The nuclease is edited out of the HIV-1 DNA sequence and the genome is then repaired by the cell’s DNA repair machinery.

“The findings are important on multiple levels,” Khalili said. “They demonstrate the effectiveness of our gene editing system in eliminating HIV from the DNA of CD4 T cells and, by introducing mutations into the viral genome, permanently inactivating its replication. Further, they show that the system can protect cells from reinfection and that the technology is safe for the cells, with no toxic effects.”

The study also addressed questions on off-target toxicity and effects. Researchers used ultra-deep whole-genome sequencing to analyze the genomes of eradicated HIV-1 cells for mutations in the genes outside the area the guide RNA targets.

This analysis was able to demonstrate that off-target effects on genes were ruled out, including any potential collateral effects on cellular gene expression.

“These experiments had not been performed previously to this extent,” Khalili said. “But the questions they address are critical, and the results allow us to move ahead with this technology.”