Biology

CRISPR gene-editing tool causes unintended genetic mutations

A new study has found that CRISPR gene-editing may have unintended genetic side effects
A new study has found that CRISPR gene-editing may have unintended genetic side effects
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A new study has found that CRISPR gene-editing may have unintended genetic side effects
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A new study has found that CRISPR gene-editing may have unintended genetic side effects
CRISPR-edited cells already underway, but this new study urges caution moving forward, suggesting we are still yet to understand the greater genomic effects of the tool
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CRISPR-edited cells already underway, but this new study urges caution moving forward, suggesting we are still yet to understand the greater genomic effects of the tool

It's not hyperbolic to say that the CRISPR-Cas9 gene-editing technique has been a revolutionary breakthrough, allowing scientists the ability to quickly, easily and precisely edit sections of DNA. But questions over how precise the CRISPR tool is have been raised in a new study from Columbia University Medical Center, which shows this gene-editing technology can introduce hundreds of unintended mutations into the genome.

CRISPR has sparked a flurry of new avenues of research around the world, from targeting cancer to HIV, with the first human trials involving CRISPR-edited cells already underway in China and a US trial slated for 2018. But this new study urges caution moving forward, suggesting we are still yet to understand the greater genomic effects of the tool.

The team of scientists involved in the study had previously been working with the CRISPR tool to treat a serious eye disease called retinitis pigmentosa, which leads to blindness. They decided to examine the entire genome of the CRISPR-treated mice from their previous experiments, looking for any potential mutations, even those that altered just a single nucleotide.

Generally, when scientists are trying to identify whether a CRISPR edit has resulted in an off-target mutation or deletion they use computer algorithms to identify areas most likely to be affected and focus their attention on those.

"These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish," says co-author of the study, Professor Alexander Bassuk, "but whole genome sequencing has not been employed to look for all off-target effects in living animals."

In examining the entire genome from the CRISPR-treated mice, they found that the tool had successfully corrected the specific gene they were targeting, but it also potentially caused a great deal of other genetic changes. In two CRISPR-treated animals, more than 100 large gene deletions or insertions and over 1,500 single-nucleotide mutations were identified.

Most significantly, all of these identified mutations were not picked up by the general computer algorithms most researchers use to look at the off-target effects of CRISPR-editing. There were no obvious or immediately deleterious effects in the animals from these unexpected mutations, but it is unknown what longer term effects the altered genes could have.

"Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations," says co-author Dr. Stephen Tsang. "Even a single nucleotide change can have a huge impact."

The team is still upbeat about CRISPR technology, but they caution other scientists to more closely study the off-target effects of any gene-editing that is undertaken. They especially note that whole-genome sequencing is vital in developing more accurate ways of using the CRISPR tool.

"We're physicians," explains co-author of the study Dr Vinit Mahajan, "and we know that every new therapy has some potential side effects but we need to be aware of what they are."

The study was published in the journal Nature Methods.

Source: Columbia University Medical Center via EurekAlert

It's not hyperbolic to say that the CRISPR-Cas9 gene-editing technique has been a revolutionary breakthrough, allowing scientists the ability to quickly, easily and precisely edit sections of DNA. But questions over how precise the CRISPR tool is have been raised in a new study from Columbia University Medical Center, which shows this gene-editing technology can introduce hundreds of unintended mutations into the genome.

CRISPR has sparked a flurry of new avenues of research around the world, from targeting cancer to HIV, with the first human trials involving CRISPR-edited cells already underway in China and a US trial slated for 2018. But this new study urges caution moving forward, suggesting we are still yet to understand the greater genomic effects of the tool.

The team of scientists involved in the study had previously been working with the CRISPR tool to treat a serious eye disease called retinitis pigmentosa, which leads to blindness. They decided to examine the entire genome of the CRISPR-treated mice from their previous experiments, looking for any potential mutations, even those that altered just a single nucleotide.

Generally, when scientists are trying to identify whether a CRISPR edit has resulted in an off-target mutation or deletion they use computer algorithms to identify areas most likely to be affected and focus their attention on those.

"These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish," says co-author of the study, Professor Alexander Bassuk, "but whole genome sequencing has not been employed to look for all off-target effects in living animals."

In examining the entire genome from the CRISPR-treated mice, they found that the tool had successfully corrected the specific gene they were targeting, but it also potentially caused a great deal of other genetic changes. In two CRISPR-treated animals, more than 100 large gene deletions or insertions and over 1,500 single-nucleotide mutations were identified.

Most significantly, all of these identified mutations were not picked up by the general computer algorithms most researchers use to look at the off-target effects of CRISPR-editing. There were no obvious or immediately deleterious effects in the animals from these unexpected mutations, but it is unknown what longer term effects the altered genes could have.

"Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations," says co-author Dr. Stephen Tsang. "Even a single nucleotide change can have a huge impact."

The team is still upbeat about CRISPR technology, but they caution other scientists to more closely study the off-target effects of any gene-editing that is undertaken. They especially note that whole-genome sequencing is vital in developing more accurate ways of using the CRISPR tool.

"We're physicians," explains co-author of the study Dr Vinit Mahajan, "and we know that every new therapy has some potential side effects but we need to be aware of what they are."

The study was published in the journal Nature Methods.

Source: Columbia University Medical Center via EurekAlert

10 comments
OleChristianHanshus
Any excuse is a good excuse to destroy the hard and excelent work of millions of researchers around the world.First they said that CRISPR was a accurate methode to insert genes,now they come with this.To cure cost a lot of efforts,but to harm takes only a spoiled nasty child.The mutations can be corrected by especial proteins made om the lab.The mutated cell dont need to be used if you cultivate in vitro.As a lot of things that could change human health for ever TODAY.And live healthier longer,much longer...
Terence Hawkes
That is not surprising. With any new technology there are always unintended consequences. It is not a question of spoiled brat syndrome as suggested by a commentor. Lets find out what the issues really are and how to prevent them. CRISPR therapy has the potential to help with horrendous diseasses.
rederje
Very fundamental research, useful, showing that we are far from understanding 4 billions years of very complex evolution of life, with DNA more or less junk, not useful at short term, but with indirect effects, strongly connected between many DNA areas, to discover, as CRISPR is using junk DNA in bacteria in reality useful. This laboratory is clearly out of lobbying, unlike OleChristianHanshus, which try to push us to believe in the perfection of CRISPR editing and on the possibility to correct theses some strange unexpected mutations between conected DNA.
yeahright
Really ..... they can't even build a diesel engine without installing cheats in it............... and you're going to try to tell me they can engineer genes correctly.......... you are either naive or uneducated
CharlieSeattle
... gene-editing may have unintended genetic side effects?? Pfft Irrelevant! I will not get the grant monet to study this if I waste time asking ethical questions, like "Just because I can, gee I wonder if I should?"
KungfuSteve
Of course, the Corrupt Chronie has to pipe up, to keep his funding / troll propaganda payments rolling in. Highly doubtful he would be healthy, and be first in line to volunteer for an enhancement test. Yet, people like this have no problem whatsoever, making the general public their unwitting test patients. And no care about all the pain, suffering, and potentially Globally Catastrophic effects that such tampering could cause. Everything from destroying our entire Immune systems, to bridging the gap for viruses to easily infect and kill Billions in a single week. From causing Incredible long term pain and mutations, to causing a person to emit toxic poison from their skin. Its pretty clear, that the Millennial generation is totally Screwed over, with Personality Disorders, Autism, and Severe allergic reactions... and its only getting worse and worse. Yet Science will keep putting TOXIC chemicals in the food, pesticides, water, sky, ground, and vaccination shots. As well as continue the use of chemical leeching plastics for food containers / cups...etc... and we see the results.. as the Females turn more masculine.. and the boys turn more feminine... and more more chaos and destruction at hand. And they also have no problem pushing their Altered foods, both Super-Hybrid wheat, as well as GMOs... which are all causing severe auto-immune responses in humans and animals... among many other problems. Go Science! Making the worlds a Complete and utter Disaster, one Screwup after another...
Millie
This new therapy promises to cure numerous diseases that have afflicted humanity for eons. In the process of developing the therapy, much more caution must be taken to not cause unintended harm. The article points out that some of the "side effects" observed were not picked up by the monitoring protocols. This is a heads up that caution must be used when continuing research, and the monitoring protocols must be expanded to look for broader unintended mutations to other DNA. As gene technology develops, we must also implement strong ethical rules and regulations globally to prevent a proverbial maniac or corporations from exploiting science to merely for profit without considering the harm to individuals or humanity from mutations.
FabianLamaestra
You have to break some eggs to make an omelet. Godspeed and continue forward. Science Never progressed by trying to make everything perfect the first time.
Mindbreaker
Every person that is born has roughly 130 mutations. Most do not do a thing, because most of your DNA does not do anything. It is stuff that was inserted by viruses and then later deactivated. Or it was random pieces of ordinary DNA that got duplicated and thrown in backward. Most of our important stuff has backward analogues in various degrees of corruption. Anything that does not work and was inserted a long time ago, may be so corrupted from so many mutations (over the generations) it is unrecognizable. Sometimes a spontaneous mutation will make something important break. That can cause the fetus to die or a person very sick. Correcting that one gene is far more important than some other random mutations that probably have a less than 1 in a hundred chance of doing any damage, that might be caused in the process. I suspect the DNA CRISPR is attracted to other than the intended target is other deactivated copies of the targeted gene backward or forward that don't do a thing. 98.8% of our DNA is noncoding. Another tenth or two does have a role, mostly assembly instructions for cells to differentiate/migrate to the appropriate location during development (though it could be a bit more, perhaps 1%). There is a chance CRISPR could reactivate some DNA that is in the wrong location making the protein the child was missing. I doubt that would cause any harm, though there is a remote chance too much could be made. CRISPR and similar tools will save thousands of lives and improve the quality of life of millions.
ljaques
Who would have thought that indiscriminate splicing of numerous genes could ever have any negative consequences? Mother Nature is obviously wrong. Full Speed webs, wings, and double heads ahead!