The study investigates the potential use of CRISPR to modify RNA. A team from Montana State University has published findings demonstrating that CRISPRs can be utilized to edit RNA, a molecule closely related to DNA. This breakthrough reveals a new method in human cells that could potentially be used to treat a wide range of genetic diseases.
Artem Nemudryi and Anna Nemudraia, alongside Blake Wiedenheft, a professor in the Department of Microbiology and Cell Biology in MSU’s College of Agriculture, conducted the research. The paper, titled “Repair of CRISPR-guided RNA breaks enables site-spec,” describes their findings.
The latest advancement in CRISPR technology, titled “Specific RNA excision in human cells,” was recently published in the journal Science. This represents the team’s continued exploration of CRISPR applications for programmable genetic engineering.
CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, is a bacterial immune system used to detect and combat viruses. Wiedenheft, a prominent CRISPR researcher, noted that while the system has been utilized for DNA cutting and editing, this new application to RNA is groundbreaking. DNA editing utilizes a CRISPR-associated protein called Cas9, while the process of RNA editing is unprecedented.
RNA necessitates the use of a different CRISPR system, known as type-III.
“In our prior research, we utilized type-III CRISPRs to modify viral RNA in a laboratory setting,” Nemudryi stated. ”However, we pondered whether we could engineer the manipulation of RNA in a living human cell.”
To investigate this question, the team engineered type-III CRISPR proteins to cut RNA containing a mutation responsible for cystic fibrosis, thus restoring cell function.
“We were confident that we could utilize these CRISPR systems to cut RNA in a programmable manner, but we were all taken aback when we sequenced the RNA and discovered that the cell had reconnected the RNA in a manner that removed the mutation,” Nemudryi explained.”In my opinion, the findings suggest that RNA repair could be a potentially important feature in human cells,” Wiedenheft commented. Nemudryi observed that RNA is constantly being replaced and destroyed within the cell, making it a transient molecule. “We had speculated that RNA might be repaired in living human cells, and it turned out to be true,” he added. Wiedenheft has been mentoring the two postdoctoral researchers for nearly six years, and he believes that their scientific contributions will have a significant and long-lasting impact.Wiedenheft stated that RNA editing could be a crucial aspect of biology and that utilizing this process could lead to new life-saving treatments. He also praised the work of scientists Artem and Anna, expressing confidence in the lasting impact of their work on humanity. According to Nemudryi, RNA editing has significant implications in the search for treatments for genetic diseases. RNA serves as a temporary copy of a cell’s DNA and can be manipulated by editing DNA, potentially causing unintended and irreversible changes. However, because RNA is temporary, any edits made are essential.
Researchers have developed a new tool for RNA editing that they hope will be as successful as the CRISPR-Cas9 method for DNA editing. The team has created a tool that allows them to study how cells repair their RNA, with the goal of using this knowledge to make RNA editors more efficient.
In their latest publication, the team demonstrates that they were able to successfully remove a mutation associated with cystic fibrosis from the RNA. However, this is just one of the many known mutations that cause diseases. The researchers are hopeful that their new RNA editing tool could potentially address numerous disease-causing mutations in the future.The new RNA editing technology will influence the future work of Nemudryi and Nemudraia as they complete their postdoctoral training at MSU and prepare for faculty positions at the University of Florida this fall. Both recognize Wiedenheft as a transformative mentor.
“Blake taught us to be fearless in testing any ideas,” said Nemudraia. “As a scientist, you should be courageous and unafraid of failure. RNA editing and repair is uncharted territory. It’s intimidating but also exhilarating. You feel like you’re on the cutting edge of science, pushing the boundaries to where no one has gone before.
