A two-punch attack from CRISPR knocks out HIV in cells

When HIV infects a person, the virus integrates its DNA into the genomes of the person’s immune system cells. Daily doses of antiretroviral drugs suppress replication of that viral DNA, but it’s not a cure.

“An ideal situation would be a single treatment, rather than lifelong therapy,” says Atze T. Das of the University of Amsterdam. In a new study, Das and colleagues report progress on a possible one-time therapy. They permanently inactivated HIV in cultured human T cells using the CRISPR/Cas9 gene-editing system to damage its DNA (Cell Rep. 2016, DOI: 10.1016/j.celrep.2016.11.057).

The technique works by designing a CRISPR component called a guide RNA to direct the Cas9 enzyme to a specific spot in an HIV gene. At that site, Cas9 cuts the DNA, and a mutation is introduced when the cell repairs the break.

Earlier this year, the Amsterdam group and researchers from Chen Liang’s lab at McGill University separately showed that cutting HIV at just one site inhibits the virus initially, but eventually HIV finds a way to continue replicating. In the new study, Das and colleagues show that using a pair of two different guide RNAs instead of one completely inhibits the virus and prevents it from escaping the cells. “We could cure the cell of HIV,” Das says.

Liang says the results are an important confirmation that attacking HIV with CRISPR is a strategy worth pursuing. “I think we can improve it if we use three or four guide RNAs,” Liang says, suggesting that could make viral escape even more unlikely.