Research on DNA repair promotes the development of gene editing technology

Now, the Princeton University researcher Britt Adamson of the new research laboratory, the Jonathan Sman Whitehead Institute member who conducted the laboratory with the collaborators, the MIT Insittute Professor of Biology and the Howard Hughes Medical Institute researcher , And Cecilia Cotta-Ramusino, this book details a new method called Repair-seq, which reveals in detail how genome editing tools work

"We have known for a long time that the mechanism of repairing damaged DNA is essential for genome editing, because to change the DNA sequence, it must first be destroyed," the senior author of the study, the Princeton University Department of Molecular Biology and the Lewis-Sigler Integrated Genome Said Britt Adamson, an assistant professor at the Institute of Science

To repair DNA, cells use many different mechanisms, each of which involves a series of genes that work together in different ways

The first author of the study, Jeffrey Hussmann, said: "Editing with double-strand breaks has been the main task of genome editing for a long time, but it is expected to be performed without unnecessary mutations.

The Repair-seq experiment produced a lot of data

In addition, a team led by David Liu of the Broad Institute of MIT and Harvard at MIT and Harvard has developed a genome editing system called "pilot editing" , Does not depend on the occurrence of double-strand breaks

Adamson said: "Cooperation is a huge benefit

The collaborating researchers found that the ability to use lead editing to obtain expected edits is affected by proteins in the DNA mismatch repair pathway

Liu said: "The cooperation with Britt, Jonathan and their laboratories is a perfect combination of basic science, tool applications, and technology development.

Importantly, this work also proves that Repair-seq can be used to improve other genome editing techniques

"Repair-seq is a perfect combination of technical wisdom and biological insight," said John Doench, director of research and development for the Broad Institute's Genetic Disturbance Program, who was not involved.

"And the work of the editor-in-chief, what a good example of cooperation!" It turns out that working with the editor-in-chief is often difficult.

In the future, the team will continue to improve the platform and apply it to other genome editing technologies

"We see Repair-seq as a tool that allows you to have a detailed understanding of the work of the genome editor in the cell, and then evaluate it very quickly,'In this environment, I can find help to improve Is the design principle of the tool?" Adamson said

These studies have been supported by the National Institutes of Health, Howard Hughes Medical Institute, Searle Scholars Program, National Science Foundation, Grants from Damon Runyon Cancer Research Foundation, China Scholarship Council and National Cancer Institute

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