Protein Tweak Makes CRISPR Gene Editing 4,000 Times Less Error-Prone (newatlas.com) 31
Researchers at the University of Texas at Austin have identified a previously unknown structure of the protein that's responsible for making edits to the wrong sections of DNA. After some tweaking, they were able to reduce the likelihood of off-target mutations by 4,000 times. New Atlas reports: CRISPR tools use certain proteins, most often Cas9, to make precise edits to specific DNA sequences in living cells. This can involve cutting out problematic genes, such as those that cause disease, and/or slotting in beneficial ones. The problem is that sometimes the tool can make changes to the wrong parts, potentially triggering a range of other health issues. And in the new study, the UT researchers discovered how some of these errors can happen. Usually, the Cas9 protein is hunting for a specific sequence of 20 letters in the DNA code, but if it finds one where 18 out of 20 match its target, it might make its edit anyway. To find out why this occurs, the team used cryo-electron microscopy to observe what Cas9 is doing when it interacts with a mismatched sequence.
To their surprise, they discovered a strange finger-like structure that had never been observed before. This finger reached out and stabilized the DNA sequence so the protein could still make its edit. Having uncovered this mechanism, the team tweaked this finger so that it no longer stabilized the DNA, instead pushing away from it. That prevents Cas9 from editing that sequence, making the tool 4,000 times less likely to produce off-target mutations. The team calls the new protein SuperFi-Cas9. The research was published in the journal Nature.
To their surprise, they discovered a strange finger-like structure that had never been observed before. This finger reached out and stabilized the DNA sequence so the protein could still make its edit. Having uncovered this mechanism, the team tweaked this finger so that it no longer stabilized the DNA, instead pushing away from it. That prevents Cas9 from editing that sequence, making the tool 4,000 times less likely to produce off-target mutations. The team calls the new protein SuperFi-Cas9. The research was published in the journal Nature.
Re: Sucks to be an early adopter of this tech. (Score:2)
Every human is a mutant.
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Trust me, there's gonna be worse side-effects from this shit than there is from nicotine.
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Do us all a favor and please don't have children after you've hacked your DNA
Humans randomly mutate at a rate of about 0.5×109 per basepair per year. The average baby has about 40 new mutations and that value is going up as parental age increases. There is no evidence that directed mutations are more dangerous than natural mutations and this new research makes editing even safer.
I have already given my daughter a list of characteristics I expect in my grandchildren. Her current BF lacks many of these features, so it looks like CRISPR is the best option.
Quote from a scientific paper [nih.gov]: (Score:2)
"Our data suggest an overall mutation rate of 2.14x10-8 per base per generation,
A lot of CRISPR won't affect reproduction at all (Score:2)
A lot of the human applications of CRISPR won't affect reproductive cells. In other words, the edits won't go into kids.
For example, the fix for cystic fibrosis mostly edits the DNA of cells in the lungs. It works, but it isn't 100%, not all the cells get fixed, just enough. Their kids would still get the unedited genes, which could pass on cystic fibrosis.
But consider this: wouldn't you *rather* that people with big genetic problems who have kids fix their DNA before having kids?
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Sickle cell is lousy protection from malaria (Score:2)
Yes, sickle cell does protect from malaria, some. But there's a "better" anti-malaria mutation. Hemoglobin C provides protection from malaria with much less disadvantage than sickle cell--though it does cause joint pain and some other more minor issues.
With the onset of medicine vs malaria, I'd say that sickle cell really is a problem.
--PeterM
This seems insanely important, and insanely good. (Score:2)
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The problem with DNA as data storage is not replication accuracy which is already "good enough", but read and write speeds.
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It is actually good enough already, before this improvement. Nobody who has been CRISPR edited so far has run into any problems due to off-target issues. So 4000x is huge. It's silly to want it to be absolutely perfect. It's like saying you won't drink water with any impurities. Well guess what all water has trace amounts of impurities. A mutation having a bad effect is very very rare. It won't happen in 99.999% of people. I mean, being born makes a person likely to get in a car accident .. does that mean n
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Considering the things it's being jury-rigged to do, high(er) level accuracy is going to be always beneficial, even the last 0.001%.
Oh goodie! (Score:2)
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Because the zombie apocalypse is caused by an intentional gene edit? 4,000 times scarier than a random mutation.
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Protein Tweak Makes zombie apocalypse 4,000 Times more likely.
4,000 times less likely. Just sayin.
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- Accidents will be less likely
- Zombie is fiction. Zombies are divided into two fictional categories:
-- Nomal zombies: There is a reason why humans stop when shot. muscles need energy and oxygen to operate. Without blood muscles don't get it and can't work. Even if zombie gene would allow to bypass this, it would still need to get the energy somewhere and only alternative for it would be to eat itself. So it would have to sacrifice muscle and fat to keep moving. It left alone, they should die in a month if
Trademarking life (Score:2)
The moving finger writes (Score:2)
And having writ, moves on. Mother nature just gave science not just the finger but the MOVING FINGER.
I'm curious. (Score:2)
We know that DNA can restructure itself via retrotransposons and that such reorganization is common within cells. (It used to be thought of as rare and an error, but it has been established that it's common and a feature, even if the purpose is unknown.) But it obviously can't happen just any old place, so there has to be a way for DNA to mark where relocatable code can be relocated to.
We also know that DNA is between 2-5% of retroviruses that have infected DNA in the past. For that to work, you'd need some
So, just like travelling to another solar system.. (Score:2)
It sucks to be an "early adopter" when messing with your genetics.
The guys who wait a bit for the technology to mature and for a body of additional facts to build up will come out ahead in the end.
For those who've missed the idea:
It's been pointed out that the first people to try to go to another star will likely do it in some sort of suspension to deal with the very long mission time... and that when they arrive and wake up, they're likely to be greeted by a civilization built by the colonists who left by