Molecular 'Lego' Promises to Sharpen CRISPR Gene-Editing Tool

Researchers have found a way to snap two enzymes together and give the DNA-snipping technique two blades instead of one.

In molecular engineering, two cuts could be better than one. Today scientists report in the Proceedings of the National Academy of Sciences on a new tool that could take the CRISPR gene-editing technique to the next level. The tool, called a "molecular LEGO," could improve CRISPR's ability to cut away damaged DNA and help treat diseases like cystic fibrosis and leukemia.

At it's most basic level, CRISPR (clustered regularly interspaced short palindromic repeats) is a way of cutting DNA at a specific spot using an enzyme called Cas9. Once the cut is made, the DNA automatically starts to repair it, causing the enzyme to cut the DNA again, initiating repair. It's a futile cycle.

"It's like you take a piece of rope and you just cut it with scissors," David Edgell, associate professor at Western University in London, Ontario, told Seeker. "The simplest thing to do is to just tape that back together, and that's what the cell's repair machinery does most of the time, it takes that break and it sticks it back together."

Edgell and his team think they found a way to stop the cycle.

"What we've done is prevent that from happening by making two breaks far apart from one another," he said.

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The researchers, including Jason Wolfs, the lead author of the paper, found a way to snap the Cas9 enzyme to an enzyme with the complicated name I-TevI nuclease domain. The resulting TevCas9 combo can be thought of as a molecular Lego with chemical blades on each end.

When used on DNA, the TevCas9 attaches to a larger segment of genetic code than Cas9 alone and instead of making a small, precise cut, TevCas9 cuts out a larger section. Removing a larger block of DNA will not only reduce the inefficient cycle of cutting and repairing, but could also prevent Cas9 from snipping unintended parts of the genome.

"Because there are two cut-sites, there is less chance that these two sites occur randomly in the genome; much less chance than with just one site," co-author Caroline Schild-Poulter, associate professor, said in a press statement.

Perfecting the technique will be essential before CRISPR or other gene-editing techniques can be used to treat diseases like leukemia, muscular dystrophy or cystic fibrosis.

Long before this new method gets approval by the FDA to treat human diseases, though, scientists will be putting their heads together to use it to understand the basic functions of DNA.

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