Crop Biotech Update

Physical Model Maps Cas9 Cutting Behavior

March 23, 2022

The path to cutting a target: the Cas9 molecule (blue) is progressively matched to its target (green) using a guide-RNA molecule (yellow). This model is derived from single-molecule experiments and structural data. When trained on biochemical data, it helps understand and predict off-targeting in probabilistic terms. (Image Credit: Martin Depken)

Researchers from Delft University of Technology (TU Delft) have developed a physical-based model that establishes a quantitative framework on how CRISPR-Cas9 works, and allows them to predict where, with what probability, and why targeting errors (off-targets) occur.

A research team led by Martin Depken at TU Delft's Department of Bionanoscience shows how the new, physical-based model greatly improves existing models not only by predicting where the DNA is likely to be cut but also with what probability this will happen. Depken's team used a physics-based approach.

“In gene editing, you want to maximize the probability of cutting at the intended site, while minimizing the amount of cutting in the rest of the genome," Depken said. They created a model that can do this. He added that their model "changes the way in which to describe the gene editing from a binary choice to a complete probabilistic picture."

For more details, read the article on the TU Delft website.

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