New "Shredder" CRISPR Technique Can Delete Large Stretches of DNA

April 12, 2019

This is a representation of how the new technique is made possible in human cells (top box) and how it acts on DNA to create long-range deletions starting at a precise point. [Zhang lab, University of Michigan]

Recently, a new article entitled "Introducing a Spectrum of Long-Range Genomic Deletions in Human Embryonic Stem Cells Using Type I CRISPR-Cas" was published in Molecular Cell journal, revealing a new gene editing tool which goes beyond the usual mechanisms of CRISPR，and that acts more like a shredder, able to target and delete much longer expanses of DNA than the current Cas9 tool is capable of.

This new tool will be used to work in genetic research to understand the underpinnings of disease, and potentially in the treatment for diseases that are associated to long stretches of DNA. The technology was also shown to work in human cells for the first time.

The tool uses Type I CRISPR-Case3, more common in bacteria than the type used in the popular CRISPR-Cas9. Type I CRISPR has never been used in eukaryotic cells, and uses a riboprotein complex for finding its target and Cas3 to shred the DNA.

Yan Zhang, Ph.D., the University of Michigan scientist who led the research, explains that the new tool 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 team worked to deliver CRISPR components into both human embryonic stem cells and into HAP1 cells. Eventually they succeeded in deleting targeted DNA sections from just a few hundred base pairs to 100 kilobases.The research was not without problems. The next job is they needed to find out what the shredder had actually accomplished using next-generation DNA sequencing and creating new methods to check the edits.