New chemical technique with CRISPR gene-editing tool helps to cure genetic diseases

CRISPR, a gene-editing technique that allows scientists to mend the DNA of human cells almost as easily as using a pair of scissors, has boosted biological and medical research in the last decade.

New chemical technique with CRISPR gene-editing tool helps to cure genetic diseases
Fu-Sen Liang. Image Credit: Case Western Reserve University.

Gene editing—particularly CRISPR, which is simple to use—has given scientists hope for curing genetic diseases like cancer.

Now, a group of Case Western Reserve University researchers has devised a way that could make CRISPR technologies even more precise—and promising.

CRISPR is combined with a chemical procedure that allows gene editing to be more precisely identified and timed, according to their new technique, which was just published in the journal Nature Communications.

According to Fu-Sen Liang, associate professor of chemistry, who lead the study team, such precision makes the device more successful and eliminates any negative effects.

While the findings are still preliminary, the researchers, which include numerous Case Western Reserve post-doctoral researchers and students, hope they will lead to more effective treatments for some diseases, including cancer.

What we are doing is exploring another way to change the outcome of the gene by targeting the RNA with a chemical. This new technology gives us the ability to target not only the place, but the time of the alteration—and the ability to stop it. That’s never been possible before, and we believe it could be very important.”

Fu-Sen Liang, Associate Professor, Chemistry, Case Western Reserve University

The technique

Clustered Regularly Interspaced Short Palindromic Repeats is an abbreviation for Clustered Regularly Interspaced Short Palindromic Repeats. The revolutionary technique, first revealed in 2012, employs a specialized enzyme directed by RNA, or ribonucleic acid, to identify, cut, and replace broken or damaged DNA strands with fresh material. All genetic information in humans and other species is carried by DNA or deoxyribonucleic acid.

The researchers at Case Western Reserve University focused on altering RNA, a polymer that performs a variety of activities such as interpreting genetic information and regulating gene activity. RNA molecules with similar genetic sequences but distinct properties and functions can be modified chemically.

The scientists were able to regulate the precise position and timing of alterations to the RNA by combining CRISPR with their chemical method.

According to Liang, this progress looks to be crucial for understanding and managing the functions of these many RNA versions in key biological processes and disorders.

Liang and colleagues utilized abscisic acid (ABA), a common plant hormone, and a technique known as “chemically induced proximity” to “write” or “erase” a structural feature known as m6A on a specific location in the RNA. As a consequence, scientists were able to switch between two different RNA variants.

According to them, scientists think that m6A alteration not only governs essential RNA processes and characteristics but is also connected to a variety of human diseases.

The study team also devised a method for turning ABA “on” using ultraviolet light, making the editing procedure much more precise, according to Liang.

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

Fu-Sen Liang, Associate Professor, Chemistry, Case Western Reserve University

Source:
Journal reference:

Shi, H., et al. (2022) Inducible and reversible RNA N6-methyladenosine editing. Nature Communications. doi.org/10.1038/s41467-022-29665-y.

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