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CRISPR 2.0 Is Here, and It’s More Precise
- deleted 9y ago[deleted]
- nether 9y agoI hope we can cure treatment-resistant depression of genetic origin with this.
- dundercoder 9y agoI have two mutations of USH2A, causing blindness. It’s a big gene. This kind of tech can’t come soon enough.
- freedomben 9y agoI too have some bad genes that make life pretty challenging at times. This type of tech gives me great hope. I wish I were more qualified to work on it and advance it.
- guelo 9y agoI'm sorry to be trying to take away your hope but I just don't see the path from CRISPR to gene therapy that can cure diseases in adults. CRISPR allows scientists to modify DNA in individual cells in a lab setting. But it doesn't help with mass editing DNA in cells throughout the body. I've heard of experiments where they take white blood cells, edit their DNA, and then reinject them. But there's currently no way to modify the genes in-place in a person's retina for example.
- freedomben 9y agoI appreciate the comment. It is certainly better to be realistic about hopes. I think my hope is really more into something like the Ray Kurzweil cellular-sized nano computers that can be injected into the body to perform various functions. As we understand what causes certain "bugs" in bodies, perhaps an effective solution can be developed.
- freedomben 9y agoForgot to add that I expect to see ads for "Company XYZ is hiring node developers to write robust and reliable javascript for our nano-computer platform" because of course the nano-bots will run javascript :-)
- rflrob 9y agoActually, the retina is one of the few places that gene therapy has been really successful. Adeno associated virus can be injected, and it has a fairly conservative safety profile (for instance, it doesn't normally integrate into the genome). https://en.wikipedia.org/wiki/Gene_therapy_of_the_human_retina https://en.wikipedia.org/wiki/Gene_therapy_of_the_human_reti... is a good place to start.
- brianberns 9y agoCRISPR can be delivered by virus to many cells of the body at once, so it seems possible that this could lead to adult therapies. https://www.quora.com/How-does-the-CRISPR-Cas9-therapy-manage-to-enter-multiple-cells-of-the-body-when-injected https://www.quora.com/How-does-the-CRISPR-Cas9-therapy-manag...
- raquo 9y agoWho needs nanobots when you can engineer viruses with such a payload. Amazing. Horrifying, but amazing.
- s4vi0r 9y agoViruses are the OG nanobots. Not only do they look robot-y, they also technically don't count as living IIRC
- 0xJRS 9y agoThere is actually a large controversy where one half of people who care think they are non living and the other half of people who care think they _are_ living.
- tormeh 9y agoLife, like free will, is just one of those words that mean less and less the closer you look. Whether they are alive or not doesn't matter.
- adventured 9y agoThat's extremely far from the truth. The entire CRISPR field is focused heavily on being able to mass edit genes in adults in fact. The three major CRISPR companies, Berkeley and Broad are all focused on pushing the technology there. It's not a question of if, it's inevitable. They already know it can be done, the challenge is scaling it up and constantly improving the accuracy and the overall command they have of what eg Cpf1 can do (in the case of Broad & Editas). A very large percentage of all disease occurs in adults after the age of ~30. That is, well after the person is an adult. Take a look at the disease targets that Editas, Intellia and Crispr Therapeutics are pursuing: they're going after adult diseases long-term, including targeting things such as diseases of the liver more near-term (next five years). Most of their initial targets are focused on easier (relative term) editing targets, the retina being a popular target due to the genes there. First they'll learn to crawl, then walk, then run. You don't have to edit all the genes in the body to cure most genetic diseases.
- Gatsky 9y agoYes, this is correct. We develop from a single cell, and many complex tissues ultimately derive from single cells. A single mammary stem cell can recapitulate the entire breast tissue for example. Bone marrow stem cells are able to produce the entire complement of red and white blood cells. If you can edit these stem cells, you will make a big difference to the patient.
- nonbel 9y ago>"That's extremely far from the truth. The entire CRISPR field is focused heavily on being able to mass edit genes in adults in fact." It doesn't seem so to me. I've noticed less and less focus on toxicity lately, as if they've given up on that. For example, I took a look at one of the papers[1] from TFA. All they look at is percent of sequences from surviving cells that contained the A->G mutation. They don't report how many cells died during the process to get there. Also, they see these mutations in the control group too (figure 4 untreated A5 = 99.8), so it seems this may be yet another way to use crispr to select for pre-existing mutants. It's hard to say since no info is provided on the toxicity for this new strategy. On the other hand, the new strategy may be less toxic since it is only supposed to introduce a single strand break rather than double (ie as opposed to cas9). Reviewers should be on this, not sure why they so consistently drop the ball regarding the role of toxicity in these studies. [1] https://www.nature.com/nature/journal/vaap/ncurrent/full/nature24644.html https://www.nature.com/nature/journal/vaap/ncurrent/full/nat...
- Geee 9y agoIs it enough to edit the genes or is there a need to activate some kind of regenerative process? The body is regenerating all the time but larger changes might require rebuilding from the ground up?
- adventured 9y agoThe very earliest targets are ideally large gene punch-out targets, using Cas9. For example that's what Editas is targeting with their first retina program. To deal with complex, higher order genetic diseases (which is also where the money will be in the field) you'll have to be able to do inserting of healthy replacement genes. Cas9 is not very good at that as of now, it's like using a mallet to tie a fishing line. There is an immense amount of effort going into trying to shoehorn Cas9 into being better at that. Other options such as Cpf1 (and possibly one day CasX/CasY from Berkeley) have been shown to be far superior at more advanced editing.
- craftyguy 9y agoHow would this help you? I don't think they could edit all of the cells required to undo this genetic defect for good, right?
- est 9y agocells in your body are being replaced every two weeks I think? There must be some way to spread the cure.
- djur 9y agoIt depends on when the gene normally expresses. Some genetic disorders result in incorrect development of organs, which means that gene therapy alone will never resolve the issue. Organ donation or surgery plus gene therapy might be a possible cure for some such disorders, though. But if a condition just results in producing too much of a hormone or something like that it could be addressed with just gene therapy.
- freedomben 9y agoOne step closer to either utopia or dystopia. I'm not sure which one.
- fratlas 9y agoutopia for some, dystopia for others?
- cycrutchfield 9y agoGenetic editing for some, miniature American flags for others!
- freedomben 9y agoThat is deep :-)
- telaelit 9y agoWhy do you think that this could cause a utopia or a distopia?
- hasenj 9y agoHow would this ever cause dystopia?
- fratlas 9y agoSeen Gattaca? This coupled with the concept of anti-aging research, interesting times lie ahead.
- brianberns 9y agohttps://en.wikipedia.org/wiki/Eugenics https://en.wikipedia.org/wiki/Eugenics
- Yuioup 9y agoMuliticlass society based on who can afford the treatment and those who can't.
- deleted 9y ago[deleted]
- Sniffnoy 9y agoWhat on earth is up with the paywall on this site? It won't let me read the non-mobile version at all.
- shafyy 9y agoWe've written a short explainer on CRISPR (if you're not familiar with the basics): https://humbot.io/How-are-designer-babies-made https://humbot.io/How-are-designer-babies-made
- rimher 9y agoHopefully this is going to be great news. I can't believe how fast the research with CRISPR is moving, and can't wait to see what's next!
- rflrob 9y agoWhile direct editing of bases will be a really useful tool, I think it's worth pointing out to any alarmists about human editing that our ability to make directed changes far outpaces our knowledge of what changes to make (and our ability to make reasonable guesses about how safe those changes are). Although there are a relative handful of diseases that have a single, protein coding change that's responsible (sickle cell, cystic fibrosis, etc), most diseases are due to multiple variants, many of which are non-coding, interacting with environmental factors and chance (diabetes, obesity, depression). These kinds of tools are incredibly useful in the lab for making advances in understanding disease, but we're a long way off from widespread clinical use, if that is even in the cards.
- beambot 9y agoOne mistake, and it could affect all of humanity in short order. Gene drives, in particular, highlight the potential potency of our ignorance: https://en.m.wikipedia.org/wiki/Gene_drive https://en.m.wikipedia.org/wiki/Gene_drive The potential for good is enormous when it comes to Gene editing. But it's not risk free. (Just like nuclear energy.)
- Ultimatt 9y agoClinical use is a when not an if http://www.nature.com/news/crispr-fixes-disease-gene-in-viable-human-embryos-1.22382 http://www.nature.com/news/crispr-fixes-disease-gene-in-viab...
- rflrob 9y agoClinical use is definitely coming, no argument there. What I am arguing is that most people don't have any medical issues that are worth the risks, expense, and ethical considerations of gene editing. I'd also doubt that will change much in the lifetime of anyone alive today.
- ilyagr 9y agoI'm more terrified of bioweapons targeted at people with some specific gene and attached to a flu virus. Genocide at a push of a button, orders of magnitude cheaper than a nuclear weapon, no materials other than standard lab equipment needed. Bond villains, rejoice! Any reason to hope we won't be able to do this for another hundred years? Because CRISPR seems awfully close.
- codq 9y agoCan CRISPR lead the bald to a full head of hair? A CRISPR hair loss cure would be worth billions.
- sschueller 9y agoI love the answer Gene Roddenberry gave regarding a bald TNG captain. At a press conference about Star Trek: The Next Generation, a reporter asked Star Trek creator Gene Roddenberry about casting Patrick Stewart, commenting that "Surely by the 24th century, they would have found a cure for male pattern baldness." Gene Roddenberry had the perfect response. "No, by the 24th century, no one will care."
- wingerlang 9y agoI don't really understand it. Is it because they have fixed it to not become bald in the first place (so no cure needed), or is he just saying no one cares about it?
- paulintrognon 9y agoBecause I guess we'll focus our futur minds on more important things than someone's baldness
- jacobedawson 9y agoMaybe by the 24th century being bald is an affectation for style's sake, and Picard is actually like a 24th century punk.
- adventured 9y agoThe solution to hair loss, in the next 20-30 years, will be cloning and implantation. Right now they do that from the parts of your head that are resistant to hair loss, using eg the FUE (Follicular Unit Extraction) approach. The obvious step from here is to clone your resistant hair follicle/s, then implant. If we can use a bioreactor to grow various organs on scaffolds now, we're going to be able to clone follicles sooner than later. I'd be surprised if some labs aren't already on this. At scale this will also be a cost-effective approach and extremely safe, it'll make gene editing as a means to combat hair loss pointless for a very, very long time.
- deleted 9y ago[deleted]
- drvdevd 9y agoThe title in Nature: “Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage” A brief description of what was accomplished (a modification of cas9): “We evolved a tRNA adenosine deaminase to operate on DNA when fused to a catalytically impaired CRISPR-Cas9. Extensive directed evolution and protein engineering resulted in seventh-generation ABEs (e.g., ABE7.10), that convert target A•T to G•C base pairs efficiently (~50% in human cells) with very high product purity (typically ≥ 99.9%) and very low rates of indels (typically ≤ 0.1%).“ Translation: they modified the CRISPR associated DNA editing enzyme, cas9, to “deaminate” (remove or otherwise alter the amino groups) in A-T or G-C pairs without breaking the DNA, as cas9 normally would. This makes single point precision edits possible, but I’m not sure what that implies for the “guide RNA” cas9 needs to know where to make the edits, as I haven’t read the paper in full yet.
- 88e282102ae2e5b 9y ago> they modified the CRISPR associated DNA editing enzyme, cas9 This is incorrect. They modified a separate enzyme that is fused to cas9.
- deleted 9y ago[deleted]
- evincarofautumn 9y agoI think that’s what they meant, and said. Cas9 “CRISPR associated protein 9” is the protein/enzyme that they modified.
- 88e282102ae2e5b 9y agoI'm definitely getting into hair-splitting territory, but I think it's important to not conflate modifying a protein with fusing two proteins. It would be easy to come away from the GP and think that scientists have the ability to easily change the enzymatic function of Cas9, when in reality they're effectively just connecting a protein to Cas9 and letting it do its thing.
- matheweis 9y agoHow are we claiming to be able to precisely edit DNA when we can’t even properly sequence it all yet - from just a couple days ago: [https://news.ycombinator.com/item?id=15534325 https://news.ycombinator.com/item?id=15534325]?
- drcross 9y ago"It’s Way More Precise", Is this good English in 2017?
- nonbel 9y agoIn case an author reads this. I tried getting the data from one of the papers: >"High-throughput sequencing data have been deposited in the NCBI Sequence Read Archive database under accession code SRP119577" https://www.nature.com/nature/journal/vaap/ncurrent/full/nature24644.html https://www.nature.com/nature/journal/vaap/ncurrent/full/nat... It doesn't seem to work (but I haven't used SRA before): >"The following term was not found in SRA: SRP119577." https://www.ncbi.nlm.nih.gov/sra/?term=SRP119577 https://www.ncbi.nlm.nih.gov/sra/?term=SRP119577