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Publications of the Week

Precise Genomic Deletions Using Paired Prime Editing

By October 20, 2021No Comments

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This week we profile a recent publication in Nature Biotechnology from first authors Choi Junhong (pictured, back row, fifth from left), Will Chen (front row, left), and the laboratory of Dr. Jay Shendure (front row, third from right) at UW.

Can you provide a brief overview of your lab’s current research focus?

The mission of our lab is to develop and apply new technologies for genetics, genomics, molecular biology, and developmental biology.

What is the significance of the findings in this publication?

CRISPR-based methods have enabled scientists to target specific locations of the genome for a variety of mutations including insertions, deletions, and substitutions, but with low precision. Recently, “prime editing”, a new method that builds on CRISPR, improved the precision of genome editing significantly but remains inefficient for introducing insertion or deletion mutations greater than 100 base pairs in size. We have developed a new method named PRIME-Del, based on prime editing, that enables the precise deletion of larger genomic regions. In our paper, we demonstrate that PRIME-Del could delete up to 10,000 base pairs with substantial improvement in precision compared to CRISPR-based methods, and allows insertion of arbitrary sequences at the deletion junction. We envision that the ability to program precise genomic deletions and rearrangements could be useful both in the precision treatment of genetic disorders involving large insertion mutations and as a tool to understand genomic function.

What are the next steps for this research?

We are interested in using this method to program multiple deletions across the genome of many cells within one experiment, in order to learn how specific deletions within the genome change how the cell functions. Such experiments could generate data to understand the function of genomic regions that we do not yet understand.

If you’d like us to mention your funding sources, please list them.

This work was supported by Howard Hughes Medical Institute, National Human Genome Research Institute of the National Institutes of Health, and the Damon Runyon Cancer Research Foundation.

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