HIV took just 2 weeks to overcome our best attempt to edit it out of our cells
A recent development brought much excitement in the scientific community. Researchers from the Francis Crick Institute in UK had announced that they had successfully removed HIV from human immune cells using a revolutionary gene editing technology called CRISPR/Cas-9 (CRISPR in short). CRISPR is a technology that works like a pair of molecular scissors to cut and paste DNA.
Worryingly though, another study has reported that HIV can evolve to survive CRISPR attacks in just two weeks. In fact, the attack by itself might be introducing mutations that make the virus stronger, researchers say.
HIV is a deadly virus that infects our immune cells. Post infection, it inserts its genome into our cells’ DNA, and then hijacks the cell to churn out more copies of itself. While antiretroviral drugs can successfully keep active HIV infections under control and extend patients’ lifespans, no one has been able to get dormant HIV DNA out of our cells, so it’s always lying in wait for the day the drugs stop. However, with the advent of CRISPR system in 2012, there was a lot of hope that it could be used to attack this dormant HIV genome and eliminate the virus from our system.
Some recent studies, like this study from McGill University, Canada, have shown extremely promising data to use CRISPR to cut up viral DNA. Thus, the virus should be effectively disabled. Unfortunately, the same group also reported that within 2 weeks, the cells started pumping out more copies of the virus. Strikingly, the virus was now stronger and resistant to CRISPR. However, the researchers involved say that the discovery is a minor setback that does not preclude the idea altogether.
Chen Liang, the lead author of the study, and his team had thought that by cutting HIV up into little pieces using CRISPR, the cell would try to patch it up (as it automatically does) and introduce ‘scar tissue’ into the sequence that would stop the virus from replicating and effectively disable it. Although, it was successful initially, some of the viruses survived and the alterations only made the virus stronger such that CRISPR was not able to attack it again.
“On the one hand, CRISPR inhibits HIV, but on the other, it helps the virus to escape and survive,” says Liang. He further adds, “The surprise is that the resistance mutations are not the products of error-prone viral DNA copying, but rather are created by the cell’s own repair machinery.”
Come to think of it, it’s not overtly surprising though. HIV has shown the ability to resist all kinds of antiviral drugs in the recent past. It does so because it is equipped with a highly error prone enzyme that copies its genome. Most mistakes stop the virus working, but occasionally a mutation is beneficial for HIV, allowing it to evade attack. But what is surprising in this instance is just how fast HIV bounced back, and the fact that our own cells seemed to have given the virus these handy mutations.
Liang still stays optimistic. “The bright side is that when you know what the problem is, you can come up with the means to overcome it,” he quips. “Just as HIV is able to escape all antiretroviral drugs, understanding how HIV escapes only helps you discover better drugs or treatments.” One possibility is to “carpet-bomb” HIV with CRISPR at many sites within its DNA instead of just the one targeted in the experiment. This, says, Liang, would make it much more difficult for the virus to evolve resistance. “Fortunately, the field is advancing very fast … I think CRISPR is easy and specific enough to use. I think we’ll see better tools [to fight HIV] soon.”
This setback might be a blessing in disguise indeed. We now know the flaws of the CRISPR/Cas-9 system, so we’ll strive to get better at using it to stop HIV for good.