A research team improves gene editing with a chemical process


CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on the ID 5AXW protein database. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)

The gene-editing technique known as CRISPR has accelerated biological and medical research over the past decade by allowing scientists to repair DNA in human cells almost as simply as using a pair of scissors.

Gene editing – and especially CRISPR, because it’s easy to use – has given researchers hope for curing genetic diseases, including cancer.

Now, a team of researchers from Case Western Reserve University has developed a method that could make CRISPR methods even more accurate and more promising.

Their new technique, detailed in a study recently published in the journal Nature Communicationcombines CRISPR with a chemical process that can more precisely locate and time gene editing.

Such precision makes the technology more efficient and reduces potential side effects, said Fu-Sen Liang, associate professor of chemistry, who led the research team.

Although the results are still preliminary, the researchers, which include several Case Western Reserve researchers and postdoctoral students, believe the work could lead to more effective treatment of certain diseases, including cancers.

“What we’re doing is exploring another way to modify the gene outcome by targeting RNA with a chemical,” Liang said. “This new technology gives us the ability to target not only the location, but also the time of the change and the ability to stop it. This has never been possible before, and we think it could be very important.

The technique

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. The transformative technology, unveiled in 2012, uses a specific enzyme – guided by RNA or ribonucleic acid – to target, cut and repair broken or damaged DNA strands with new material. DNA, or deoxyribonucleic acid, contains all genetic information in humans and other organisms.

Case Western Reserve scientists focused on manipulating RNA, a polymer with various functions, including translating genetic information and regulating gene activity. RNA molecules can have various chemical modifications with identical genetic sequences but different properties and functions.

By combining CRISPR with their chemical process, the scientists took control of the precise location and timing of RNA changes.

This breakthrough appears to be key to understanding and controlling the roles of these different RNA versions in fundamental biological processes and disease, Liang said.

Specifically, Liang and his team used abscisic acid (ABA), a common plant hormone, and a process called “chemically induced proximity.” This allowed them to either “write” or “erase” a structural feature called m6A onto a specific area of ​​the RNA. As a result, they could effectively switch between two versions of RNA.

Scientists believe m6A modification regulates fundamental RNA processes and properties, but is also directly linked to various human diseases, he said.

The research team also created a way to use ultraviolet light to activate ABA, making the editing process even more precise, Liang said.

“What makes the research even more exciting is that we believe it can be applied to other RNA modifications, not just m6A,” Liang said, “and the functions of the vast majority of these modifications are totally unknown.”

Team develops method to increase gene editing efficiency while minimizing size of DNA deletions

More information:

Huaxia Shi et al, Inducible and reversible editing of N6-methyladenosine RNA, Nature Communication (2022). DOI: 10.1038/s41467-022-29665-y

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Case Western Reserve University

Research team improves gene editing with chemical process (2022, May 16)
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