HIV can become resistant to CRISPR/Cas9 gene editing just as with antiretroviral (ARV) treatment, Genomeweb reports. Publishing their findings in the journal Cell, researchers led by Chen Liang, PhD, of McGill University used the cutting-edge CRISPR/Cas9 editing technique to snip key portions of HIV’s genetic material out of infected cells.
This new study raises questions about research out of Temple University published in March that showed success in using CRISPR/Cas9 to snip the entire HIV genome from immune cells. (That study spawned a rash of erroneous headlines that claimed a cure might be only three years off.)
During the CRISPR/Cas9 editing process, a so-called guide RNA locates the HIV DNA in the CD4 cell. Next a nuclease enzyme cuts the strands of immune cell DNA, editing out the HIV DNA sequence. Then the cell’s own repair mechanism melds the loose DNA strands back together.
The researchers who published in Cell found that a CRISPR/Cas9 method that cut out a key portion of HIV’s genome—the researchers tried going after various portions, but not at the same time—was successful at killing many copies of HIV. However, some virus evaded the attack. These investigators also tried using the same technique as the Temple researchers to snip out the entire viral genome but still found that some virus was able to get around the treatment and become resistant.
After analyzing DNA sequences, the researchers found that the virus had developed mutations quite close to the spot in the genetic chain that the Cas9 enzyme had been instructed to cut. The investigators theorize that, after the DNA strain was snipped, slight errors that the cell’s repair process introduced resulted in a viral genome that was able to replicate and infect other cells. In particular, this particular strain virus can infect immune cells that have undergone the same gene editing, and is also resistant to further attacks from the gene-editing therapy.
Scientists from this and other similar studies believe that, just as with combination ARV treatment, a multipronged gene-editing treatment—one that knocks out several fundamental HIV genes at the same time—may be necessary to avoid such mutations that confer viral resistance. Elsewhere there is research that looks to make immune cells resistant to HIV in the first place, as with trials that use a different gene-editing method, called zinc-finger nucleases. This approach would be less likely to lead to resistance.
To read a Nature letter about the study, click here.
To read the study abstract, click here. To read the Nature letter, click here.
To read the GenomeWeb article, click here.