Science

New CRISPR gene-editing tool removes cells' natural undo button

New CRISPR gene-editing tool r...
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The new CRISPR enzyme, TevCas9, will be able to make cuts to DNA in two places at once
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The new CRISPR enzyme, TevCas9, will be able to make cuts to DNA in two places at once
The Western University researchers behind the new CRISPR technique, Caroline Schild-Poulter, David Edgell, and Greg Gloor
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The Western University researchers behind the new CRISPR technique, Caroline Schild-Poulter, David Edgell, and Greg Gloor
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The CRISPR-Cas9 gene-editing tool promises to radically change how disease is treated, with potential for tackling muscular dystrophy, HIV and retinal degradation, among others. Now, scientists at Western University in Ontario have edited the editor, adding a new engineered enzyme to CRISPR that can help prevent the target DNA from repairing itself and canceling out the desired changes.

With human trials kicking off recently, CRISPR's power comes from the ability to let scientists swap out sections of DNA, removing unwanted genes like those that might cause cancer or other diseases, and splicing in more helpful ones. Unfortunately, cells have a natural ability to fight back against the "damage" to their DNA molecules, which may undo the benefits.

"The problem with CRISPR is that it will cut DNA, but then DNA-repair will take that cut and stick it back together," says David Edgell, principal investigator of the study. "That means it is regenerating the site that the CRISPR is trying to target, creating a futile cycle. The novelty of our addition is that it stops that regeneration from happening."

The new CRISPR enzyme, TevCas9, will be able to make cuts to DNA in two places at once
The new CRISPR enzyme, TevCas9, will be able to make cuts to DNA in two places at once

The addition in question is an enzyme called I-Tevl, which is combined with Cas9, the DNA-cutting enzyme that gives the CRISPR-Cas9 tool its name. But where Cas9 only makes cuts in one site on the genome, the newly-created TevCas9 cuts in two places, making it much harder for the cell to repair.

As an added bonus, using TevCas9 appears to reduce the chances of unwanted side effects as a result of the cutting, by targeting genes much more directly.

"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," says co-author, Caroline Schild-Poulter. "This remains to be tested, but this is the hope and the expectation."

The research was published in the Proceedings of the National Academy of Sciences.

Source: Western University

4 comments
guzmanchinky
Incredible science. I just don't know what else to say, I'm so amazed by these advances.
VirtualGathis
There is a word missing in there, "Temporarily"... This sentance: "The novelty of our addition is that it stops that regeneration from happening." should read "The novelty of our addition is that it stops that regeneration from happening temporarily." if this tech is going to be anything but a sci-fi horror story. Without the DNA repair system in place the conversation with your doctor would go like this: DR: Well we cured your cancer, and made you immune system resistant to it so relapse is unlikely. Patient: Great! So smooth sailing and good health from now on? DR: Well, about that... We had to use cripr-cas9 with the repair inhibitor, so you no longer have cancer, but it will only be six months to a year before the affected tissues begin to break down in much the same way as they would if you'd been exposed to excessive radiation...
michael_dowling
Incredible indeed. Having lost a relative to cancer,I hope this turns the tide against a cruel disease.
habakak
So......Crispr-Cas9 is not the miracle it was touted to be? Miracles don't exist and Crispr-Cas9 is not going to be the miracle we thought it would be. Things inevitably end up being way more complicated than we anticipated. It will help. It might do some wondrous things. But it won't be easy, cheap and without consequences.