Gene Editing Technology Removes HIV from Animal Genomes

CRISPR/Cas9 gene editing system shows promise eliminating HIV.

In a breakthrough discovery, investigators successfully excised a segment of HIV-1 DNA from the genomes of animals using gene editing technology.

This technology is based on the CRISPR/Cas9 gene editing system. In earlier studies, researchers were able to demonstrate the ability to eliminate HIV-1 from infected cells in vitro with no adverse effects on the host cells.

Ex vivo experiments that used clinical specimens, including T cells taken from HIV-positive patients that were expanded in culture, revealed that viral replication was significantly reduced after treatment with the gene editing system.

The current study, published in Gene therapy, sought to determine whether the gene editing technology could eliminate HIV-1 in transgenic rats and mice where the HIV was incorporated into the genome of every organ and cell in the animals.

A recombinant adeno-associated viral (rAAV) vector delivery system was used to deliver the technology to the living animals’ cells.

The gene editing was also engineered to cleave the integrated HIV-1 DNA in the host cell genome, resulting in the excision of the viral DNA from the host genome.

Two weeks after the rAAV CRISPR/Cas-9 molecules were delivered into the bloodstream, the tissue DNA from the animals were analyzed. The results of the study showed that the targeted segment of HIV-1 DNA had been excised from the viral genome in every tissue, including blood cells, the brain, heart, liver, kidney, spleen, and lungs.

In the rat model, researchers analyzed viral RNA and revealed that the strategy was able to significantly reduce HIV-1 RNA levels in the circulating lymphocytes and lymph nodes. This indicated that the excision of the viral genome had a significant impact on the HIV-1 expression in cells that carried integrated viral DNA.

“The ability of the rAAV delivery system to enter many organs containing the HIV-1 genome and edit the viral DNA is an important indication that this strategy can also overcome viral reactivation from latently infected cells and potentially serve as a curative approach for patients with HIV,” said lead study investigator Kamel Khalili, PhD.

The strategy used in the study eliminated all opportunities for the development of replication-competent virus and escape.

This gene editing technology could potentially be used alone to eradicate HIV-1 DNA from patients, as well as used in combination with antiviral drugs to help further the suppression of viral RNA. Additionally, the technology could also be adapted to target mutated strains of HIV-1.

Next, researchers plan to conduct a follow-up study that used a larger group of animals. However, a clinical trial could happen within the next several years, the study authors noted.