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FDA approves first test of CRISPR for genetic defect causing sickle cell disease
- The_rationalist 6y agoIf CRISPR can be bruteforced to change a significant number of cells for a whole organ/body then what is stopping us from rejuvenation? (store your DNA in while not too old in a safe place fill this DNA in tons of virus vectors/CRIPRs and hop you can be rejuvenated!)
- Vecr 6y agoProbably not, killing off your bone marrow cells and replacing them is already pretty dangerous, and other organs would be way worse, because they have actual structure. Doing it with your brain would be impossible, for obvious reasons.
- stjohnswarts 6y agoBig if true.
- deleted 6y ago[deleted]
- xiphias2 6y agoHasn't Vertex already run an experiment on people and cured sickle cell disease using CRISPR last year? What's new here (except that the organizations are different)? https://sicklecellanemianews.com/ctx001-sickle-cell-disease https://sicklecellanemianews.com/ctx001-sickle-cell-disease
- maxerickson 6y agoThat trial deactivated a gene (causing a different one to be more active). This trial is inserting/editing a gene.
- xiphias2 6y agoThanks!
- DoreenMichele 6y ago“We are motivated to work toward a cure that can be accessible and affordable to patients worldwide,” Sickle Cell is prevalent in some populations because the gene mutation is protective against malaria. (Probably only beneficial if you have one copy, not two.) I hope they will keep this in mind and work to eradicate malaria hand-in-hand with trying to eradicate the genes that are protective against it when they look to take it global.
- XorNot 6y agoWe're a hair's breadth away from using genetic engineering to make the mosquito extinct. We have the technology (gene drive) but scientists just aren't sure if we should do it.
- DoreenMichele 6y agoThey are right to have concerns. There was an island where they used poison to kill all the mosquitoes because it was a big problem. All the mosquitoes dies and then all the things that ate the mosquitoes died. And then all the things that ate things that ate mosquitoes died. And it went through a few more layers of this, like some modern day version of the Biblical plagues. That doesn't mean we shouldn't do it. It just means it is correct to not take the decision lightly. (Unfortunately, I've never found a good write up of this true story on the internet. I read it long ago back when dinosaurs roamed the earth and I had a bright yellow rotary phone and got information printed on dead trees.)
- est31 6y agoYou don't have to extinguish all mosquito species. It's enough to only target those which can carry diseases. Ideally one would engineer mosquitos to avoid humans because of their smell.
- bamboozled 6y agoMaybe we could also considering modifying ourselves to be less susceptible to mosquitos. Including helping people who live in poverty to have better housing and medicine so their less susceptible to Malaria ?
- pastrami_panda 6y agoFor those interested in CRISPR tech I'd highly suggest reading up on BEAM therapeutics. It's base pair editing which makes it much more precise compared to CRISPR which is editing DNA chains. They don't have editors for all base pairs yet but they have a couple and it looks very promising.
- jfarlow 6y agoThe Base Editor (and Prime Editor, etc.) _is_ CRISPR (Cas9) but with additional components fused to it that provide it additional features allowing it to edit in a more elegant way over the naked Cas9. https://serotiny.bio/notes/proteins/sabe4gam/ https://serotiny.bio/notes/proteins/sabe4gam/
- jonplackett 6y agoSo CRISPR now has frameworks? Cool.
- godmode2019 6y agoCan someone answer, what is the entry method of CRISPR in adults, don't it need to change all instances of a cell to be effective? I don't really understand the delivery method.
- azernik 6y agoBrute force: "...some of the patient’s hematopoietic stem cells... [are] harvested for gene editing outside the body. After these cells are removed, the remaining bone marrow is destroyed with chemotherapy to allow space for the repaired and reinfused stem cells to grow." EDIT: This is apparently the same procedure as conventional bone marrow transplants in SCA patients. CRISPR is just slotted into that workflow to synthesize a transplant, without needing to find a donor.
- grapecookie 6y agoBro if it actually uses chemo to destroy your marrow and then grafts new youGM marrow? thats Frankenstein and evil af.
- liamwire 6y agoEven with the amount of hype around CRISPR, that is... incredible. Turning patients into their own donors feels magical. I suppose in this instance, the patients wouldn’t need immunosuppressants after their treatment, as I’d expect standard care patients currently need for life?
- rcthompson 6y agoI think it's an open question. After this treatment, the patient's red blood cells will be producing a new protein that they have never produced before. This protein only differs from the previous one by one amino acid, so the question becomes how sensitive the immune system is to such a change. Given that the immune system has some difficulty recognizing cancer cells with multiple protein-coding mutations in them, I think it's likely that a single amino acid change will fly under the radar and not require any immune suppression, at least for the vast majority of recipients of this treatment.
- o0-0o 6y agoVery cool. Now please, work on Myelo Fibrosis next!
- jostmey 6y agoI've learned a lot about gene therapy. The immune system is a major bottleneck to wide spread gene therapy. If you modify the genetic makeup of cells in your body, the immune system will recognize the new antigens being presented by these cells and attack. Many gene therapy target point mutations that don't require significant alterations to correct that would alarm the immune system.
- f6v 6y agoIt’s also that we don’t have organism-scale models of how change in one gene will affect other body functions. We don’t know how to build these kind of models and we don’t have even 1% of the data to do that. Organoids are just emerging, but they aren’t 1:1 representation of what happens in real human.
- amelius 6y agoDon't point mutations cause proteins to fold differently? And thus causing the proteins to become globally different rather than locally different?
- jostmey 6y ago1. Most point mutations won't result in significant changes, but if we are talking about gene therapy, the specific point mutation probably did effect protein folding or function 2. Proteins in each cell are broken down into unfolded fragments and presented on major histocompatibility complexes as antigen.
- keven 6y agoFor people interested in Crispr, Rich Horgan started a non-profit called Cure Rare Disease working to fast-track customized therapeutics for his brother and other families with Duchenne Muscular Dystrophy using in-vivo gene editing. https://cureraredisease.org/ https://cureraredisease.org/
- yarcob 6y agoTLDR: 1) Extract bone marrow from patient 2) Use CRISPR to fix broken gene in the extracted bone marrow 3) Use chemo to destroy old bone marrow in patient 4) Transplant fixed bone marrow from step 2 back into the patient
- yarcob 6y agoThe technique sounds promising, since it avoids the typical problem of gene therapy, which is how to get CRISPR past the immune system into every cell in the body. With this technique you can do the CRISPR procedure in vitro. A big downside to this treatment is that as far as I know this kind of chemo can make male patients infertile.
- doubtfuluser 6y agoFor my understanding: crisper works by cutting the dna at specific points surrounding the relevant part and then exchanging, right? How likely is it, that in the whole DNA string there are other instances this “surrounding” matches and would be cut? How is this prevented / not causing side effects?
- julienreszka 6y agoDNA has something like "Bytes" Clustered Regularly Interspaced Short Palindromic Repeats
- yarcob 6y agoThe nice thing about CRISPR is that you can use pretty long sequences for matching, so in theory you can just pick a sequence that doesn't occur anywhere else and cut there. (Before CRISPR, you would use restriction enzymes with a short, fixed recognition sequence, typically 4-6 base pairs [1]. In that case it was a bit tricky to find the right enzyme that cuts the DNA in the right place, and not in an unwanted place. And you couldn't just cut the DNA in any place you want.) [1]: https://en.wikipedia.org/wiki/List_of_restriction_enzyme_cutting_sites:_A https://en.wikipedia.org/wiki/List_of_restriction_enzyme_cut...
- pmlnr 6y agoI honestly thought my generation will not yet live through Gattaca; seems like I was wrong.
- koonsolo 6y agoHelping people with severe diseases is still far away from creating the perfect humans. You turning this positive into a negative is distasteful.
- pmlnr 6y ago> Helping people with severe diseases is still far away from creating the perfect humans. Not as far as it looks. Honestly, it looks closer, than real self driving cars. > You turning this positive into a negative is distasteful. I'm incredibly happy that we, as humanity, are advancing with science - the mRNA vaccines are also incredible. The part that is not incredible is that we, as society, are in most cases still behave like we did in the stone age: greedy, selfish, narcissistic. Because of this tech that should be used to help those in need is most commonly used to "help" those with enough funds or means. Cheering for science advancements that are far out of reach for the majority leaves a bitter taste. EDIT BTW, Gattaca is a temporary time. Once it's passed - one whole generation, so say ~80 years - that world would be wonderful, but that limbo time, when the movie plays out, is the nasty part.
- boxed 6y ago> Cheering for science advancements that are far out of reach for the majority leaves a bitter taste. Yes. Damn that new fancy tech of farming that only the rich can afford! Seriously. Think about what you're saying for a second. Tech that is only for the rich becomes affordable for the masses faster and faster every year. Computers were for nation states in my parents life time. Today there are computers more powerful than the first computers in cheap toys. We cheer for tech that only the rich can use now because it will be for the masses soon. Tech that never exists for the rich, will not exist for anyone ever. Check your logic.
- vagrantJin 6y agoYeah. My one and only concern is how tight regulation around genetic augmentation/editing will be. When will medical use cross over into cosmetic use and how do we regulate that?
- faeyanpiraat 6y agoWell you wont be able to prevent rich people from getting their regular life extension treatments.
- f6v 6y agoYou can already do a plastic surgery. So how is genetic editing to make yourself hotter different?
- doggodaddo78 6y agoIs there more than one cause of sickle cell?
- dagurp 6y agoI really hope this will be successful. Does anyone have an idea how much a treatment like this would cost?
- f6v 6y agoA wild guess: million+. It’s supposed to be a once in a life time treatment, so pharma can’t milk you for life. It’s not that pharma is inherently bad, but rather that it costs billions to get this through all the stages of clinical trials.
- codeproject 6y agoTwo years ago, Chinese Scientist Dr.He JianKui did a very similar thing. He edited the genome of twin girls so that they will be immune to the HIV-virus. By all account the project is successful. The announcement of this breakthrough causes a lot controversies. People are shocked and dismayed. Here is the link: https://www.nature.com/articles/d41586-018-07545-0 https://www.nature.com/articles/d41586-018-07545-0
- meepmorp 6y agoUsing CRISPR to edit the genomes of human embryos because YOLO, is very different to using it in a modified version of an existing treatment for sickle cell anemia. Do you not see the difference in ethical scale and scope?
- WaitWaitWha 6y ago>Do you not see the difference in ethical scale and scope? I agree with you that to you (and me) in this case there is a difference. But, who sets the scale & scope? (I am aware that the box has been opened, it will never be closed.)
- codeproject 6y agoTotally Agree!!! it is the initial stage.
- downrightmike 6y agoHIV is a very capable mutator, all he did was give it a chance in two hosts to mutate against. and then who knows the future danger of the kid's health. Dolly the sheep was cloned, but had enlarged organs. So not perfect. And what changes in these kids is a huge unknown and there was no way to predict it, because the doc just did because he could. Plus a whole eugenics program has a huge historical negative example in the last century because it lead to death camps.
- 542354234235 6y ago>But, who sets the scale & scope? Whoever does it, hopefully it is after evidence-based discussions to establish a framework for ethical and safe application. Just because the box can’t be closed doesn’t mean we just throw our hands up and say “well, nothing we can do to steer this in a responsible direction”. We don’t breed humans like dogs to produce super men, even though we theoretically could.
- mrfusion 6y agoSo how do they get the crispr into the cell and into the cell nucleus? Would fixing scd be all or nothing?
- meepmorp 6y agoThe treatment is basically a bone marrow transplant, which would typically use donor cells from another person; CRISPR lets you use the patient's marrow instead, hopefully reducing rejection and other issues. You extract marrow and CRISPR it to get rid of the problem gene. Then you kill off all of the bone marrow in the patient, and replace it with the new stuff. That's a cure.
- nerdkid93 6y agoI was super pumped for this tech to start being used in human clinical trials, but a couple of years ago, there was a study[0] that raised some key concerns about CRISPR therapeutics increasing the risk of cancer due to some edited cells self-destructing once their genomes have been modified, leaving behind cells with a higher risk of cancer due to not being as sensitive to genomic edits. Have these challenges been overcome yet? [0]: https://www.scientificamerican.com/article/crispr-edited-cells-linked-to-cancer-risk-in-2-studies/ https://www.scientificamerican.com/article/crispr-edited-cel...
- suifbwish 6y agoWoah! So the cells that accept the CRISPR modifications do so because they have dysfunctional p53 gene activation. This most likely means they are specifically the cells most likely to become tumors if they undergo any mutations triggering carcinogenesis as p53 and its helper genes are mainly responsible for killing off cells that become cancerous among other things. This means that you can use CRISPR to selectively kill these cells only since they would be the only ones that easily accept and express the CRISPR modifications. This could be ground breaking if it is not already tried.