CRISPR-Cas9: Scientists Discover How to Improve Gene Editing Precision

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A team of researchers from Kyushu University and others has solved a problem in CRISPR-Cas9, a technology that allows the modification of an organism's genome (complete genetic information) at will. 

It was made possible by a new technology that improves modification precision by a factor of 3000. The researchers hope to put the technology to use in a few years to aid in safe gene therapy. The team announced its achievement in a British journal on April 11.

DNA (deoxyribonucleic acid) is the main body of the genome that represents genetic information with a chain of bases. CRISPR-Cas9 cuts DNA at targeted locations, or inserts chosen sequences of bases. The technology consists of a substance that serves as a guide to the target site and an enzyme that acts as scissors to sever the DNA. 

But the issue with CRISPR-Cas9 was that its cutting ability was too strong. That meant the enzyme would also cut off non-target areas.

Crucially, the researchers discovered that adding cytosine to the guiding substance reduced its ability to bind to and cut DNA. They realized that properly regulating the number of cytosines increased the accuracy of cutting the targeted area by a factor of 19. 

Reducing the Risk of Cell Death

Cuts in the wrong location could cause cells to die. However, the majority of cells were unaffected in the team's experiment, increasing safety by 1800 times. Furthermore, the technology's precision in modifying only the targetted genetic information was improved by a factor of 3,000.

These issues are unimportant when successful results can be selected from a large number of genome editing experiments. But when one is unable to select in this way, it causes serious problems. 

Gene therapy using CRISPR-Cas9, for instance, is undergoing clinical trials overseas. However, it has been linked to the risk of cancerous cell transformation caused by off-target cuts. 

But Dr Masaki Kawamata, assistant professor at Kyushu University, is confident that the team's new technology will help solve the problem:

"We have already applied for a patent and formed a venture company to put the technology into practice in society. We hope to begin gene therapy clinical trials in about a year and have it ready for use in a few years."

About CRISPR-Cas9

CRISPR-Cas9 is a genome editing technology developed in 2012 by American biochemist Jennifer Doudna and French professor Emmanuelle Charpentier. The technology is simpler to use than previous methods, and its popularity has grown. In 2020, both were awarded the Nobel Prize in Chemistry for their contributions to major advances in life science research. 

Expectations are growing for applications in the medical field, such as gene therapy. Additionally, in Japan and elsewhere, research is advancing toward the practical use of genome-edited foods with enhanced nutritional components.

This article was first published on JAPAN Forward on April 20, 2023.

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