Montana State University researchers recently published their findings demonstrating how RNA can be edited using CRISPRs, revealing a new human cell process that could be used to treat a variety of genetic diseases. The research demonstrates a novel use for CRISPR, which previously had only been used to edit DNA.
Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR, has been used for years to cut and edit DNA using the CRISPR-associated protein Cas9. To date, using CRISPR to edit RNA is unprecedented and will require a different CRISPR system called type-III.
“In our previous work, we used type-III CRISPRs to edit viral RNA in a test tube,” said Artem Nemudryi a postdoctoral researcher. “But we wondered, can we program manipulation of RNA in a living human cell?”
In the research, published in Science, the team used type-III CRISPR proteins to cut RNA containing a mutation that is responsible for cystic fibrosis ultimately restoring normal cell function.
“We were confident that we could use these CRISPR systems to cut RNA in a programmable manner, but we were all surprised when we sequenced the RNA and realized that the cell had stitched the RNA back together in a way that removed the mutation,” said Blake Wiedenheft, professor in the Department of Microbiology and Cell Biology at MSU.
“People used Cas9 to break DNA and study how cells repair these breaks. Then, based on these patterns, they improved Cas9 editors,” said Anna Nemudraia a postdoctoral researcher. “Here, we hope the same will happen with RNA editing. We created a tool that allows us to study how the cells repair their RNA, and we hope to use this knowledge to make RNA editors more efficient.”
While the research demonstrates the ability to mitigate cystic fibrosis mutations, that is only one of the potentially thousands of known mutations that lead to the disease. Future expansion of the technique could address additional mutations, as well as expand to encompass an array of additional genetic diseases potentially paving the way for new lifesaving treatments for a myriad of diseases.
“The work done by Artem and Anna suggests that RNA repair might be a fundamental aspect of biology and that harnessing this activity may lead to new lifesaving cures,” said Wiedenheft. “Artem and Anna are two of the most brilliant scientists I have ever encountered, and I’m confident that their work is going to have a lasting impact on humanity.”