CRISPR-Cas9 is a revolutionary genome editing tool, and scientists at MIT have figured out a way to make it even more precise than ever before.
Genetic editing opens the door to a huge range of possibilities; from helping correct for hereditary diseases to possibly even programming human traits ahead of time, the power of the world’s first pair of genetic scissors, the CRISPR-Cas9 editing system, could not be understated.
According to a report from Phys.org, a group of researchers from the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have made a major breakthrough in CRISPR editing techniques, significantly lowering the number of errors that the tool was recently prone to make.
The tool works by targeting specific sequences in a cell’s DNA and altering them based on the instructions coded in the Cas9 protein. It alters the DNA at a location specified by an RNA molecule, with a sequence that matches the target site.
Cas9 has been shown to be highly effective at editing genetic information at the target site, but it has been notorious for snipping other sequences unintentionally. This can lead to a number of unexpected or undesired edits in a cell, which could potentially have devastating effects.
The paper, published in the journal Science, showed that by changing just three of roughly 1,400 amino acids that form the Cas9 enzyme from a bacteria S. pyogenes, “off-target” editing was reduced to undetectable levels.
The study, led by Feng Zhang, drew on knowledge about Cas9’s structure to determine where off-target edits were most likely to occur. Negatively charged DNA binds to a slit in the Cas9 protein, which carries a positive charge. Researchers predicted that by replacing certain positively charged amino acids with neutrally charged ones, off target edits were reduced by a significant amount.
The new enzyme, called “enhanced” S. pyogenes Cas9, or eSpCas9 for short, has greatly improves the accuracy of the CRISPR method. This could have far-reaching implications for researchers hoping to edit specific genes to produce desired outcomes in humans, animals, and plants.
According to Professor Zheng, “Many of the safety concerns are related to off-target effects. We hope the development of eSpCas9 will help address some of those concerns, but we certainly don’t see this as a magic bullet. The field is advancing at a rapid pace, and there is still a lot to learn before we can consider applying this technology for clinical use.”
A press release from the Broad Institute of MIT and Harvard outlining the details of the study can be found here.