New DNA Editing Technique Outstrips CRISPR/Cas9 Many Times Over

Researchers have developed a new tool for gene-editing that is being compared to a DNA “shredder” called CRISPR/Cas3, able to edit long sequences of DNA with programmable alterations.

Introducing CRISPR/Cas3

Geneticists at the University of Michigan (UM) and Cornell University have developed a new DNA editing tool that can be programmed to edit longer stretches of DNA than is currently possible using CRISPR/Cas9 gene-editing.

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Called CRISPR/Cas3, this new system has the potential to revolutionize disease research, according to UM’s Yan Zhang, Ph.D., an assistant professor of biological chemistry who led the research.

"Cas9 is a molecular scissor that goes where you want it and snips once," said Zhang. "But Cas3 goes where you want it, travels along the chromosome, and makes a spectrum of deletions tens of kilobases long. This could make it a powerful screening tool to determine what large areas of DNA are most important for a particular disease."

The potential lies in the ability for researchers to experiment on long stretches of DNA without knowing precisely which gene in the entire genome they need to target. With CRISPR/Cas3, they could simply alter entire stretches of DNA and see what happens.

How CRISPR/Cas3 Works

Referred to as a “shredder,” the comparison is an apt one. Unlike the scissoring characteristic of CRISPR/Cas9, CRISPR/Cas3 moves along the entire length of the designated stretch of DNA and “shreds” the underlying material.

Both the CRISPR-Cas-9 and CRISPR/Cas3 systems are borrowed from bacteria, but the Cas3 variety uses a Type I CRISPR, which is more common in bacteria than the Type II CRISPR used in Cas9. According to UM—who has co-patented the technique alongside Cornell University—, “Type I CRISPR has never been used in any eukaryotic cells, and employs a riboprotein complex known as Cascade for seeking its target and an enzyme called Cas3 for shredding DNA.”

The research was published in Molecular Cell.