Just last month, scientists managed to use a revolutionary gene-editing technique to remove the HIV genome from infected human cells. Unfortunately, a new study published in the journal Cell Reports reveals that HIV is able to quickly adapt to this type of gene-editing attack by mutating, allowing it to evade destruction.
“In some ways, it may not seem surprising that HIV-1 is able to escape from [gene-editing attacks],” the authors note. After all, the virus can already quickly “develop resistance to antiviral drugs, immune responsiveness, and other types of pressure.” Although this new discovery is clearly a setback, the researchers insist that the idea of editing out HIV is still viable.
Although genetic editing traditionally takes a lot of time and effort, the rise of CRISPR-Cas9 has sent shockwaves through the scientific community. Since it emerged in 2012, this technique allows the rapid alteration of the DNA of any organism, including humans.
After using bacterial enzymes to “snip” genomes at precise spots, geneticists can then insert customized genetic material wherever they wish. Researchers have since decided to use this technique to fight against HIV, a notoriously incurable viral infection.
HIV, like all retroviruses, have their genetic code in the form of RNA, sometimes seen as the primitive precursor to DNA. It infects T cells, a type of white blood cell, by inserting a DNA-based replica of its own RNA into the cell’s genome. The infected cells then produce copies of this genome, which then attack new cells as fully-fledged HIV entities.
Using CRISPR-Cas9, however, the team were able to locate and remove the entire HIV genome from infected T cells with no adverse effects to the cells themselves, which continued to grow and divide as per normal. In addition, these T cells appeared to be immune to new infection by HIV later on.
The gene-editing technique has been shown to be both effective and ineffective against HIV, depending on how it’s deployed. science photo/Shutterstock
For this new study, a team of virologists and geneticists chose a variation of this technique. Instead of giving T cells immunity to viral infection, they actually bequeathed to them genes designed to seek and destroy HIV pathogens themselves. By giving these cells DNA-shearing enzymes called Cas9, along with customized pieces of RNA that let the enzyme identify specific parts of the HIV genome, they effectively created a T cell equipped with an HIV-destroying homing missile.
Regrettably, two weeks after the team first equipped the T cells with this genetic weaponry, they noticed that the very same cells were producing copies of HIV that appeared to have escaped the gene-editing attack. They discovered that the virus had produced new defensive mutations right near the genetic sequence the Cas9 enzyme was designed to snip away.
Anything with a genome undergoes genetic mutations, and although many can be bad, some are beneficial, giving the host an evolutionary advantage. In much the same way, the HIV here appears to have mutated when it was faced with the Cas9 attack.
In this instance, it appears the virus was able to mutate in such a way that left the virus still able to infect T cells. These mutations made the surviving HIV unrecognizable to the T cells, meaning that this mutated HIV was even more resistant to attack than before.