On Monday, scientists at UC Berkeley’s Doudna Lab published research on a new system for targeting RNA sequences using clustered regularly interspaced short palindromic repeats, or CRISPR, an adaptive immune system present in bacteria, paving the way for additional research and potential medical use.
The system, dubbed “CRISPR-Csm,” can target RNA sequences more effectively than previous systems and reach RNA both inside and outside of a cell’s nucleus, according to David Colognori, first author of the paper and postdoctoral fellow in the Doudna Lab.
“CRISPR exists in bacteria,” said Colognori. “These CRISPR RNAs serve as antibodies, basically; they’re specific and they specifically recognize and bind to the viral DNA or RNA.”
CRISPR cuts those viral DNA and RNA sequences in bacteria, Colognori said, a strategy that has been employed for biotechnological uses.
The new system, which Colognori worked on with bioinformatician Marena Trinidad and principal investigator Jennifer Doudna, founder of Doudna Lab, is able to target more RNA sequences more efficiently than previous methods, which cause “collateral damage,” Colognori noted.
“CRISPR-Cas13 is the only other known RNA cutter,” Colognori said. “In the past few years, people have been noticing that Cas13 doesn’t only cut the intended target that you designed the CRISPR RNA to, but it also starts shredding a bunch of other RNA in the cell.”
According to Colognori, CRISPR-Csm also differs from many CRISPR systems because it is composed of multiple proteins, while systems such as Cas13 are single proteins. Systems with multiple proteins have largely been avoided because they are seen as more complex and more difficult to use in human cells, he said.
Colognori acknowledged that CRISPR-Csm may be more difficult to apply to animals compared to cells in a lab dish because it is composed of many parts, but he hopes that it will be used in the future for therapeutics.
“It worked as well as or better than other single protein systems like Cas13,” Colognori said. “That showed proof of principle that these multicomponent systems aren’t actually as difficult as people thought and that they are actually very harnessable as tools.”
CRISPR-Csm has important implications for research, he noted – it is a new research tool for people studying RNA, especially RNA inside a cell’s nucleus. Additionally, targeting RNA with CRISPR-Csm will enable better RNA imaging, allowing researchers to visualize RNA in live cells.
When studying RNA, CRISPR is often used to “delete” the RNA, which is an important part of the research process, Colognori said.
“This is a new research tool that will allow people that study RNA to delete their RNA much easier,” he said. “It can also be used for targeting viruses because a lot of viruses are made of RNA.”