DNA-Based Bacterial Parasite Uses Completely New DNA-Editing Method 20
Scientists have uncovered a new gene-editing tool with potential to rival CRISPR, according to studies published in Nature on Wednesday. The system, based on a bacterial DNA parasite called IS110, uses RNA guides to target specific genomic locations. While showing promise for precise DNA cutting, the method currently lacks the accuracy needed for human applications. At best, it achieved 94% accuracy in lab tests. The team also revealed the molecular structure of IS110's DNA-cutting enzyme, shedding light on its unique four-step editing mechanism.
Nature, 2024. DOI: 10.1038/s41586-024-07552-4, 10.1038/s41586-024-07570-2.
Nature, 2024. DOI: 10.1038/s41586-024-07552-4, 10.1038/s41586-024-07570-2.
Re:Yeah, cause it's worked so well for CRISPR (Score:5, Insightful)
Until the 2000s, no US President has lived past age 92 -- zero. Since then, 4 presidents have done so. It takes a couple decades from concept to clinic because of all the FDA process. One example, CAR T-cells treatment for cancer. It was first proof of concept in 1989 ( https://www.ncbi.nlm.nih.gov/p... [nih.gov] ) and a human didn't get proven effective until 2013 ( https://pubmed.ncbi.nlm.nih.go... [nih.gov] ). Today CAR T-cells are curing cancer.
This adds significant cost and overhead to any novel treatment development. If society was willing to risk lives to develop cures (we absolutely should NOT btw), we'd have these treatments faster. Anyway the huge delays and the $2.3 billion cost (https://www.genengnews.com/gen-edge/the-unbearable-cost-of-drug-development-deloitte-report-shows-15-jump-in-rd-to-2-3-billion/ ) to develop ONE DRUG from lab to clinical trial (which can fail and then you lost all that money) makes people afraid to invest in ideas. I mean, would you put $2.3 billion into something not sure if it will pay off? This isn't like throwing a penny in a slot machine. Anyway, gene editing (CRISPR or most likely some other way is too compelling to ignore). Keep in perspective, it took 125 years to go from telephone to smartphone.
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About the $2.3 billion cost .. if you think that's not a big deal .. have you ever had an idea for a website or some cool product .. and you just needed about $100,000 investment .. you know how hard it is to pitch that to investors and get them to write you a check? And that's is even if you can show you'll have at least a few customers and almost guaranteed partial ROI. Yeah .. now try pitching for $2.3 billion for something where investors know they could lose the whole $2.3 bil .. zero ROI and maybe eve
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mRNA was discovered back in the 1960s and wasn't researched much until the 1990s. Only a few years ago did they use it to make a successful vaccine.
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Good thing we've got all these new miracle cures from CRISPR CAS9, now let's add another way to cause cancer, uhm, I mean cure diseases. Oh, wait, it's all still experimental and really hasn't done anything for the average person at all. This from the tech that in 2012 claimed was going to be revolutionary and cure nearly all genetic diseases. I realize there has been some progress on Beta-Thalassemia (Sickle-Cell) and LCA, but slow, grinding, research-paper progress isn't really what was promised was it?
I just heard about an exciting scientific breakthrough on the news this morning.
It's mid-afternoon already, why hasn't that breakthrough turned into tangible household products yet!?!?
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> It's mid-afternoon already, why hasn't that breakthrough turned into tangible household products yet!?!?
Haha, look at those losers who didn't cure cancer before lunch! Nerds.
I don't know what a restriction enzyme is but I sure feel morally superior.
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Show me any time locked promise anyone of scientific standing (somebody with a PhD in science and/or who is respected in the field) made about CRISPR.
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Re:Yeah, cause it's worked so well for CRISPR (Score:4, Interesting)
12 years isn't an afternoon and they made big promises which are still just promises. They have next to dick to show normal people the value of these wonderful discoveries after 12 years.
It is for medicine. You need to understand the tech, play with it in microorganisms, then play with it in animals, watch it play out for a bunch of years to make sure there's no weird side effects, then create your therapy, test in animals again, then do the human trials, and then finally get approval.
And it sounds like they just approved a treatment that could help a significant fraction of people with sickle cell anemia [scientificamerican.com] which is pretty substantial.
By comparison they've been working on mRNA therapies since 1989, and Moderna was founded in 2010. So yeah, it typically takes a lot of years for these technologies to turn into therapies.
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You: No it doesn't, you only waited an afternoon!
Me: More like 12 years
You: That's basically an afternoon for medicine
Me: Thanks, I have no more questions your honor.
Objection to the title (Score:2)
"Newly discovered" not "new".
Re:Objection to the title (Score:4, Informative)
Years ago one of my coworkers bought a car, and another coworker asked him if it was new. The first coworker had the perfect answer: "It's new to me."
Sounds interesting (Score:2)
Emphasis on "potentially." The problem is that the targeting sequences in the loops are quite short, with the insertion site targeted by a recognition sequence that's only four to seven bases long. At the short end of this range, you'd expect that a random string of bases would have an insertion site about once every 250 bases.
That relatively low specificity showed. At the high end, various experiments could see an insertion accuracy ranging from a close-to-being-useful 94 percent down to a positively threatening 50 percent. For deletion experiments, the low end of the range was a catastrophic 32 percent accuracy. So, while this has some features of an interesting gene-editing system, there's a lot of work to do before it could fulfill that potential. It's possible that these recognition loops could be made longer to add the sort of specificity that would be needed for editing vertebrate genomes, but we simply don't know at this point. ...while the IS110 system may not be accurate in terms of the sites it recognizes, it appears to be very precise in terms of what it does after they're recognized. Which would be a nice feature if we could boost the accuracy.
So we've found a new system for editing DNA, but it can't be used as is because the RNA target is too short. If the RNA can just be made longer that would be easy, but if the protein only works on a short section of RNA then there's little chance of using it broadly anytime soon.
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There's definitely more engineering work to do -- but it's worth working on. It took a 125 years to go from telephone to smartphone and thousands of ideas in between.
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Well, not long after ... https://web.archive.org/web/20... [archive.org]
Re:Sounds interesting (Score:4, Insightful)
But if its inserting its payload into the wrong spot, that's a bigger more urgent problem. It also doesn't say whether the P53 or DNA damage response is activated, whether the cell goes through apoptosis as a result (crispr-cas9 edits have this problem) https://www.nature.com/article... [nature.com] https://doi.org/10.1158/0008-5... [doi.org]
Right now maybe this tool could be used to initiate apoptosis through DNA damage response or P53 activation (by altering and thus 'damaging' the DNA). But as the studies said, the cells that survive the edits are p53 mutated and that happens in about half of cancers. Some serious hurdles to overcome if they want to edit and repair DNA.
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I assumed a longer RNA would also be more accurate, as more bases should mean a stronger bond, as well as greater specificity. Maybe temperature or buffer solution could improve the accuracy if those were suboptimal. Other than that, I doubt there's anything else they could do.