HIV Can Elude CRISPR/Cas9 Technology

The CRISPR/Cas9 gene editing tool has been making headway in the research field with no signs of slowing down, but a recent study published in the Cell Report states that more work needs to be done to better target HIV.

CRISPR/Cas9 can be programmed to target a DNA sequence and split viral DNA. Although many viruses are able to be killed with this targeted approach, some are able to elude the treatment, resulting in the virus becoming more difficult to target.

“When we sequence the viral RNA of escaped HIV, the surprise is that the majority of the mutations that the virus has are nicely aligned at the site where Cas9 cleaves the DNA, which immediately indicates that these mutations, instead of resulting from the errors of viral reverse transcriptase, are rather introduced by the cellular non-homologous end joining machinery when repairing the broken DNA,” said senior study author Chen Liang.

These mutations can vary in size and have the ability to hide from Cas9.

“Some mutations are tiny--only a single nucleotide--but the mutation changes the sequence so Cas9 cannot recognize it anymore,” Liang said. “Such mutations do no harm to the virus, so these resistant viruses can still replicate.”

The study results serve as a warning for those who hope to use CRISPR/Cas9 as an antiviral, however there are strategies that can be used to overcome these limitations.

“CRISPR/Cas9 gives a new hope toward finding a cure, not just for HIV-1, but for many other viruses,” Liang said. “We have a long road toward the goal, and there may be many barriers and limitations that we need to overcome, but we're confident that we will find success.”