The CRISPR gene-editing tool may be one of the most important medical breakthroughs in decades, but there's still plenty of room for improvement. Although Cas9 has been the go-to enzyme for gene-editing, that doesn't mean it's necessarily the best option. Now a team of scientists, including the co-creator of CRISPR, has engineered a more precise enzyme, known as Cas12b.
CRISPR works on the genome like a pair of scissors, allowing scientists to target specific DNA sequences – say, those that raise your chances of certain diseases – then snip them out and replace them with more beneficial genes. The enzyme Cas9 has traditionally done the heavy lifting, by binding to the target and performing the required edits.
But it's not flawless. Concerns have been raised in the past that Cas9 isn't picky enough, with the potential to cause unintended mutations in other parts of the genome, and may increase a patient's cancer risk. Although some studies pointing out these problems were later retracted, it's still not a bad idea to investigate alternatives in case safer options are out there.
And Cas12b might just fit the bill. The researchers say the new enzyme is smaller and can home in on targets more precisely than Cas9, and they demonstrated its prowess by editing primary human T cells. As the foot soldiers of the immune system, fine-tuning these cells could improve a whole range of immunotherapy treatments.
"This is further evidence that there are many useful CRISPR systems waiting to be discovered," says Jonathan Strecker, first author of the study.
Although Cas12b was identified as a CRISPR candidate as far back as 2015, it wasn't easy to get it up to scratch. This enzyme is sourced from bacteria that prefer hot environments like volcanoes and deep sea hydrothermal vents, so it operates at temperatures higher than the human body. To find a version that could work under cooler conditions, the team scanned the genetic sequences of thousands of bacteria, eventually settling on one found in a bug called Bacillus hisashii.
To speed up progress, the researchers have freely opened up the CRISPR-Cas12b system to academic teams everywhere.
The research was published in the journal Nature Communications.
Source: MIT