New CRISPR enzyme mutation proves almost 100 times more precise

The CRISPR-Cas9 gene editing system is an extremely powerful tool, but there are still a few kinks to iron out. One of the main problems is off-target edits, which can have serious consequences. Now, researchers have found a particular mutation of the CRISPR enzyme that’s almost 100 times more precise than the most commonly used one.

So the new study, led by researchers at Wenzhou Medical University in China, set out to investigate if there were more precise versions of the enzyme. To investigate, the team generated many different mutations of Cas9, then tested how well they were able to single out a target sequence among very similar – but wrong – sequences.

And sure enough, they found what they were looking for. One mutation in particular stood out, for being able to filter out mismatches that differed from the desired target by as little as one base pair. The team says that this makes it as much as 93 times more precise than the original enzyme.

On closer inspection, they also managed to figure out why it was so much better. Basically, the mutation affects the recognition domain of the enzyme, which worked to weaken the contact between the guide RNA and Cas9. That means that it takes a much stronger pairing to trigger the cut – effectively ensuring that only the correct sequence would do the job.