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Escape From Editing

A study involving a T-cell line has shown that HIV-1 can become resistant to CRISPR/Cas9 editing, as GenomeWeb has reported.

Researchers led by McGill University's Chen Liang found that the CRISPR genome editing approach can target and excise viral DNA that has integrated into the host genome, but also that mutations emerged in the viral sequence targeted by the guide RNA that then enable the virus to escape from editing, as they write in Cell Reports this week.

"This is what is happening in tissue culture. If Cas9 is used to treat patients with HIV-1, this will happen again," Liang tells GenomeWeb.

That the virus was able to escape editing isn't entirely unexpected, Nature News adds, as HIV has been able to develop resistance to a number of drugs. Liang says that he and his team think the resistance crops up when Cas9 cuts the viral DNA and the host cell tried to repair the damage. Rather than introducing an indel that inactivates the viral genome, he says the viral genome could be left intact or a sequence change that made the region unrecognizable could be introduced.

However, Liang and his colleagues note in their paper that targeting multiple sites in the viral genome is a possible way around the problem, as is using a different nuclease that cuts upstream of the targeted regions, as GenomeWeb notes.

"In the beginning everything is great," Liang tells GenomeWeb. "But when you start to know more and more, things often get more complicated."