Although scientists are hopeful that the CRISPR/Cas9 gene-editing platform will be an effective antiviral, a new study reveals that HIV can overcome this gene-editing attack. A team of researchers found that when they used CRISPR/Cas9 to mutate HIV-1, despite some single mutations inhibiting viral replication, others led to unexpected resistance.
When HIV enters a cell, its RNA genome is converted into DNA and becomes integrated into the cellular DNA. CRISPR/Cas9 can be used to target a specific DNA sequence and snip the viral DNA, making it a potentially effective antiviral.
The problem revealed in the new study is that HIV can use new mutations to survive and thrive, meaning some viruses that escape the CRISPR/Cas-9 treatment will be much more difficult to target than those killed by the approach.
"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 Chen Liang, senior author of the study and professor at McGill University AIDS Centre.
"Some mutations are tiny - only a single nucleotide - but the mutation changes the sequence so Cas9 cannot recognize it anymore," he said. "Such mutations do no harm to the virus, so these resistant viruses can still replicate, he says"
The team believes that one solution could be targeting multiple sites with the CRISPR-Cas9 gene-editing platform or using other enzymes as an alternative to Cas9.
"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."
However, some other researchers believe that using CRISPR/Cas9 to genetically modify a large number of T cells to combat HIV might not be the best method of fighting the virus, instead suggesting that the increasing number of antiretroviral drugs being created are a much more feasible solution.
The findings were published in the April 7 issue of Cell Reports.
