CRISPR 'gone wild' has made stocks swoon, but studies show how to limit off-target editing
The fear that CRISPR-based genome repair for preventing or treating genetic diseases will be derailed by "editing gone wild" has begun to abate, scientists who are developing the technique say. Although there are still concerns that CRISPR might run amok inside patients and cause dangerous DNA changes, recent advances suggest that the risk is not as high as earlier research suggested and that clever molecular engineering can minimize it.
"Progress is being made at a pretty stunning rate," said biochemist David Liu, of Harvard University and the Broad Institute, who has developed several versions of CRISPR. A parade of new discoveries, he said, "suggests that it's possible to use these genome-editing tools and not make unintended edits."
Upgrade makes genome editor CRISPR more muscular, precise
Many groups are trying to do better, and now, a team led by chemist David Liu at Harvard University has engineered a version of CRISPR that potentially is both more dexterous and more precise.
[...] The new work, reported online in the 28 February issue of Nature, modifies the Cas9 enzyme, creating at least four times as many potential docking sites. In theory, this could allow researchers to, say, cripple or replace many parts of genes associated with human disease that CRISPR currently cannot touch.
Evolved Cas9 variants with broad PAM compatibility and high DNA specificity (DOI: 10.1038/nature26155) (DX)
Preprints:
- NmeCas9 is an intrinsically high-fidelity genome editing platform (open, DOI: 10.1101/172650) (DX)
- No unexpected CRISPR-Cas9 off-target activity revealed by trio sequencing of gene-edited mice (open, DOI: 10.1101/263129) (DX)
- In vivo CRISPR-Cas gene editing with no detectable genome-wide off-target mutations (open, DOI: 10.1101/272724) (DX)
- High-precision CRISPR-Cas9 base editors with minimized bystander and off-target mutations (open, DOI: 10.1101/273938) (DX)
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One of the barriers to using CRISPR-Cas9 gene editing in the clinic is the possibility that the enzyme will clip DNA in the wrong spot. In a study published in Nature [DOI: 10.1038/s41586-018-0500-9] [DX] today (September 12), researchers describe a strategy to predict these off-target mutations throughout the genome and show in mice that a carefully designed guide RNA strand does not produce any detectable slip-ups.
The study confirms that "you'd better make sure that you've got a really accurate guide RNA," says Janet Rossant, a developmental biologist at the University of Toronto and the Hospital for Sick Children who did not participate in the work. "This [method] is a better way of testing for how specific that guide RNA will be before you go into animal models and, of course, into humans," she adds.
According to coauthor Marcello Maresca, a biologist at AstraZeneca in Sweden, one long-term goal of his company is to be able to use therapeutic gene editing to address a number of human diseases. "However, realizing the potential of CRISPR medicines requires the development of methods to enable the efficient modification of the target gene with no effects elsewhere in the genome," he writes in an email to The Scientist.
VIVO = "verification of in vivo off-targets".
Related: CRISPR Safer than Thought; Misleading Study Found Shared Mutations in Closely Related Mice
CRISPR Becomes More Precise
Paper That Found CRISPR "Off-Target Effects" Retracted
Repair of Double-Strand Breaks Induced by CRISPR Leads to Large Deletions and Complex Rearrangements
Did CRISPR Really Fix a Genetic Mutation in These Human Embryos?
(Score: 1) by cocaine overdose on Monday March 12 2018, @02:07PM
(Score: 2) by Justin Case on Monday March 12 2018, @02:08PM (1 child)
We are well acquainted with phones you merely rent, videos you don't own, tractors you can't modify... soon it will come to this: do you own your DNA code or will you have to get permission to edit it?
Sure, the CRISPR technique may be the intellectual property of those who have developed it, but imagine a day when you have the tools to modify your DNA. Will you be allowed to make yourself much stronger or smarter? Apply "personal software updates" that haven't approved yet by your masters? Adjust your pleasure sensors, or modify the production of adrenaline to make yourself a more aggressive combatant?
Or will "they" decide what software updates you need, and require them all to be applied every Patch Tuesday, without even telling you what they're changing?
(Score: 0) by Anonymous Coward on Tuesday March 13 2018, @01:00AM
If you don't have an NDA with your medical provider, you are already screwed.
They can do whatever they want, whenever they want with ANY samples taken from your body. Keep that in mind the next time the FBI DOESN'T need a DNA sample from you... because they already have it on record because of your regular visits to the doctor.
For anyone who doubts this, around the turn of the millenium there was a row about this in Texas I believe, where they were taking DNA samples from the children without the parents permission and using them to create a genetic database of all new children born at multiple hospitals there.
If they were doing that 20 years ago, what aren't they telling you they are doing now?