Researchers at USU, in collaboration with colleagues at the University of Texas and the Helmholtz Institute in Germany, have published two back-to-back papers in this month’s volume of Nature, on a new CRISPR system called Cas12a2. Unlike the more well-known CRISPR Cas9, Ryan Jackson, lead author on the papers and assistant professor of biochemistry at USU, said the protein machinery of Cas12a2 cuts multiple types of nucleic acids.
“In both papers we show that this machine can cut double-stranded DNA, single-stranded DNA and RNA. But, it stays off, it doesn't do any of that until it becomes active. So there's an 'on' switch. We show in 3-dimensional detail how this molecular changes its shape to go from the 'off' to the 'on' position,” Jackson said.
The CAS12a2 system was discovered in a sulfur-loving bacteria that inhabits mines and caves. Jackson said that like all CRISPRs it’s used by the bacteria to fight off virus invaders. What makes CAS12a2 unique is that when turned on, it shuts down the host cell.
“When our machine detects a virus through detecting its virus RNA, instead of it cutting just that RNA, it just turns on this crazy activity that starts cutting all the DNA in the cell, which basically it does destroy the virus, probably, but also shuts down that cell so that the cell cannot be used to make more virus. And so this shutting down of the cell, instead of protecting the cell was a huge paradigm shift in how people think about what CRISPR does in nature,” Jackson said.
Jackson said these characteristics hold exciting possibilities for the field of medicine. For example, Cas12a2 could be used to selectively target problematic cells and then shut them down, such as in infections and cancer.
