21 ms·

CRISPR gene-editing breakthrough opens door to treating broad array of diseases

600 points by hassanahmad 5y ago

toomuchtodo 5y ago
Off topic: are there any central repositories tracking gene therapy progress for various genetic conditions, with a similar UX to Moderna’s mRNA pipeline tracker? https://www.modernatx.com/pipeline https://www.modernatx.com/pipeline
- t3po7re5 5y ago
  All FDA trials are listed here: https://clinicaltrials.gov/ https://clinicaltrials.gov/, I believe you can search by gene. It's not as nice as the moderna pipeline though.
  - DSingularity 5y ago
    Thanks for that!
Causality1 5y ago
I must be out of the loop. Last I heard trials with CRISPR were making not only the desired genetic changes but also dozens of others at random points in the genome. Did they solve that problem?
- dsign 5y ago
  Humans improve technology all the time, CRISPR gene editing would be no exception. Straight from Wikipedia: https://en.wikipedia.org/wiki/LEAPER_gene_editing https://en.wikipedia.org/wiki/LEAPER_gene_editing I bet a dip into the specialized papers will show a multitude of these techniques.
softwaredoug 5y ago
The period missing from the title makes this very hard to parse what is being said.
- caymanjim 5y ago
  Agreed. NPR never used to use clickbait titles like this ("He ..." is pure clickbait). It's sad to see them doing it regularly now. I imagine the latest generation of journalists grew up thinking this is normal. I know HN prefers original headlines, but I wish these would be edited down when posted here.
  - mjfl 5y ago
    "well then stop clicking on them!"
    - caymanjim 5y ago
      I often say the same thing myself. I expect it on CNN, and I do passively protest by ignoring links like this most of the time. NPR usually has good articles behind the links, and I'm more inclined to hold my nose and click if they make it to HN. In this case, the actual article is good. I'm lamenting the negative trend.
hmmmhmmmhmmm 5y ago
Original paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2107454?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2107454?query=fe... This is the first published IV-administration of a gene-editing CRISPR payload. Interesting convergence with the nanoparticles used in mRNA vaccines. Sickle-cell and immune reprogramming edits have been made on cells removed from the body. Josiah Zayner infamously injected himself with CRISPR at a conference years back, but (1) unpublished, AFAIK and (2) he had been drinking which likely attenuated the payload [and (3) he wanted bigger muscles, not to treat a disease]
- gwern 5y ago
  Mirror: https://www.gwern.net/docs/genetics/editing/2021-gillmore.pdf https://www.gwern.net/docs/genetics/editing/2021-gillmore.pd...
DrAwdeOccarim 5y ago
Wow, it worked...This uses LNPs similar to the recent Moderna and BioNTech/Pfizer vaccines, and N1m-pseudouridine mRNA, just like the mRNA vaccines. This is incredible.
changoplatanero 5y ago
Reminds me of this guy that cured himself of lactose intolerance. https://www.popularmechanics.com/science/health/a17804128/scientist-painstakingly-documents-his-own-diy-gene-therapy/ https://www.popularmechanics.com/science/health/a17804128/sc...
- stuntkite 5y ago
  His YouTube channel The Thought Emporium, is amazing. He just moved into a new lab and I really appreciate what he’s working on and how he communicates it. The robot painting fluorescent proteins is neat and recently he dropped a video demonstrating his adventures making synthetic opal. Apparently the edit made him totally lactose tolerant for over a year and now he has very mild lactose intolerance. He says he hasn’t redosed because he wants to improve the plasmid (I think that’s the right term, BUGFIX probably isn’t right) before he takes another run at it. Here’s his update video from last year on that endeavor. https://www.youtube.com/watch?v=aoczYXJeMY4 https://www.youtube.com/watch?v=aoczYXJeMY4
  - faitswulff 5y ago
    Technically a plasmid is kind of like a software patch, but generally they're employed by bacteria and not eukaryotes like humans.
    - stuntkite 5y ago
      Interesting. I have watched nearly all of The Thought Emporium’s videos (so clearly I’m an expert, lol) and I think he uses the term plasmid to describe DNA he’s working on in the crazy bio IDE he uses. I think in this instance he applied it to a yeast that he cultured and put into pills and swallowed. He really is doing some neat stuff though. He’s inspired me to do some small bio hacking experiments and it ALMOST makes me want to go back to college.
      - shpongled 5y ago
        Plasmid is the correct term!
xwdv 5y ago
What are the limits of gene editing?
- xf1cf 5y ago
  A better question might be what are the ethical limits of gene editing. How long until we stumble over eugenics but with extra steps? It seems to me at least to be the natural conclusion of advanced gene editing. Law of unintended consequences and all that.
- stuntkite 5y ago
  I don’t think there are any aside from money, time, and experience. If you’d like to give yourself glowing purple eyes, huge muscles, and make it so you fart clouds of illegal street drugs you can but it’s much more difficult and messy than deleting ‘node_modules’, rebuilding, and doing a `git push —force` into prod at 5PM on a Friday before you take a long weekend.
- wizzwizz4 5y ago
  We're constrained by the subset of physics that can be implemented by proteins. Plus, the genetic code can't be too big, or it won't fit, but I doubt we'll ever hit that limit (provided we don't go the software route and build a giant tower of massive abstractions that gets copied everywhere).
  - hoseja 5y ago
    Proteins and things built by proteins. Teeth aren't very protein-y.
    - xwdv 5y ago
      Why can’t we hardwire genes to continue growing teeth?
      - hoseja 5y ago
        Because we have specialized diverse teeth. Of course it's possible but that would be novel genetic programming which we just can't do.
DudeInBasement 5y ago
Cool, we can only show stories where it worked
- carbocation 5y ago
  Human clinical trials are pre-registered, in order to prevent exactly what you are describing (the 'file drawer problem').
  - DudeInBasement 5y ago
    Not in all countries, just ask CCP
- wesleywt 5y ago
  Coming from a genetics background, I can tell you the fact that it worked once is a massive achievement in itself. This is science fiction.
zz865 5y ago
Would CRISPR be the technology people would use to modify a bat virus to make it human transmissable? This stuff should stay in its box.
- kyriakos 5y ago
  Knives can kill and save people. Almost anything can be used for bad purposes in the wrong hands.
  - newsbinator 5y ago
    Not that I agree we should bury our heads in the sand like luddites, but to be fair to OP, knives can only hurt or help in a tiny human radius. It's hard to make an extinction-level weapon (or extension level accident) out of them. Being able to edit genes at will is a different story.
    - wizzwizz4 5y ago
      Viruses are an extinction-level weapon. CRISPR? Not so much. (And neither are likely to result in an extinction-level accident; you'd have to deliberately deploy potent bioweapons in multiple places to extinct us.)
      - deleted 5y ago
        [deleted]
      - SavantIdiot 5y ago
        Yes but the CRISPR engine is passed on to offspring which raises massive ethical questions. As I understand it (and hopefully I'm not way off base here) there is a technique that creates a "gene drive" which is kinda like an SDK that is inserted into the patients genome which improves the efficacy of CRISPR. This code finds its way into the gametes which is then passed on to children. The children did not ask for this SDK, but now they have it and it potentially becomes immortal in human DNA. On the one hand, cool: the SDK is there and possibly makes it even easier to alter DNA> On the other hand, holy shit: there's a ticking timebomb in the populations DNA now. It's called CRISPR-cas9: https://wyss.harvard.edu/media-post/crispr-cas9-gene-drives/ https://wyss.harvard.edu/media-post/crispr-cas9-gene-drives/ https://scicomm2020.wordpress.com/2020/02/24/controversial-gene-drive-system-found-to-fight-antibiotic-resistance/ https://scicomm2020.wordpress.com/2020/02/24/controversial-g...
calrueb 5y ago
The fact that we can apply these sort of therapies to an adult human who consists of millions upon millions of cells blows my mind. Having the ability to fix our "buggy" genetic code while we are alive is amazing.
- hhjinks 5y ago
  You're off by a _couple_ orders of magnitude. There are trillions of cells in a human body.
  - hoseja 5y ago
    10^6 * 10^6 = 10^12
- correcthorse123 5y ago
  I think targetting tbe liver is far easier than most other tissues though, unfortunately.
  - dclowd9901 5y ago
    Gotta start somewhere...
- rorykoehler 5y ago
  Monkey patching in production.
BurningFrog 5y ago
So this is editing liver cells, which I read somewhere is the easiest to do, since the liver absorbs foreign elements from the bloodstream. The success of this should mean that many genetic liver conditions can soon be treated this way. For other organs, I expect a longer wait.
- codeulike 5y ago
  The brain is particularly hard due to blood/brain barrier, crispr is too big a molecule to go through. So might need injections into cerebral spinal fluid for that
- wgolsen 5y ago
  The lung epithelium has also recently been transfected in humans (see Translate Bio cf drug; this and similar vehicles can deliver editing tools)
foreigner 5y ago
This is awesome but I'm curious why they tried it first on this super-rare disease instead of something more common?
- inglor_cz 5y ago
  My 2 cents: a) need to edit liver cells only, not the entire organism, b) the disease is deadly, so the patients do not have much to lose if anything goes wrong.
- Turing_Machine 5y ago
  Wild guess: it's because he's 65. Many of these severe genetic diseases kill their victims at relatively young ages. Ethical researchers are thus far being super-cautious about modifying the genome of someone who's likely to have children. While the article doesn't say, I wouldn't be surprised to learn that he has explicitly agreed not to have any (more?) children.
- SoftwareMaven 5y ago
  Extremely rare diseases and diseases that have no known treatment options are given more lax rules for testing. Without that, there would be no way to develop treatments for them, but it comes with a side benefit of providing a method to attempt new treatment modalities.
palijer 5y ago
I feel like I missed something, and now everywhere I look we have headlines like this. What's wrong with "CRISPR gene editing shown to cure Transthyretin amyloidosis in patient study" Maybe I'm now one of the old people who doesn't understand new usage of language. But I understand that usage dictates grammar rules, but I feel I missed something.
- dogma1138 5y ago
  NPR isn’t a research paper, or a researcher focused website.
- eat_veggies 5y ago
  The paper linked in the article is titled "CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis." That's close enough to your proposed title. If what you're looking for is a technical research paper meant for people intimately familiar with the field, then that's a great title. But it's a terrible title for an article meant for laypeople like us. The words "transthyretin amyloidosis" are utterly meaningless to me and most HN/NPR readers, but "He Inherited A Devastating Disease" tells me what kind of disease it is (devastating, heritable) and why CRISPR gene editing might be a big deal. It also helps clue me into the contents of the article. Because it is as much a summary of a key research result, as it is a profile of Patrick Doherty, a man affected by the disease. That's entirely missing from your title. None of this is new. "Write for your audience" is as old as writing itself.
- ben_w 5y ago
  I think it’s just an oddity of newspapers. Even before it was called “going viral”, they’ve been a bit like that.
- phreack 5y ago
  I know what you mean. These headlines read less like titles and more like lyrics in a song ("He was a skater boy. She said see you later boy."). It feels a bit condescending, as if it was aiming at children. I'd much prefer a title with a "person with thing does action" style.
- boublepop 5y ago
ausbah 5y ago
>Doctors infused billions of microscopic structures known as nanoparticles carrying genetic instructions for the CRISPR gene-editor into four patients in London and two in New Zealand. The nanoparticles were absorbed by their livers, where they unleashed armies of CRISPR gene-editors. The CRISPR editor honed in on the target gene in the liver and sliced it, disabling production of the destructive protein. this is one of the coolest paragraphs I've read in a while. if it's accurate, serves as a great reminder that we're in the future as we speak
- DoctorNick 5y ago
  The record breaking temperatures that I'm suffering in the PNW right now serves as a grim reminder that we won't have much of a future, even with all this cool tech.
  - cj 5y ago
    It’s not impossible to speculate the possibility that in 50-100 years, climate change could be reversed through a CRISPR-like technology (e.g. something that can be released and replicate in the environment, thereby changing it). Or at the very least, I can see a future where gene editing could relieve your suffering from heat by raising the threshold your body can tolerate :)
    - nr2x 5y ago
      At current rates of carbon outlay, there won’t be much of a world left to save in 100 years.
      - pkdpic_y9k 5y ago
        Not unless we all work our asses off! Engineers can do anything :^)
        matmatmatmat 5y ago
        ... except politics, engineers are usually not very good at politics, and climate change is, in large part, a political problem.
iandanforth 5y ago
Please do familial hypercholesterolemia soon! I know it would be harder but getting started on targeting specific mutations could be fruitful. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681164/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681164/
- bigmattystyles 5y ago
  I want the CRISPR research that focuses on CIP accelerated. I have a minor chronic pain issue that will get worse over time (think sciatica). By the time I’m 60 in 25 years, it’d be great if we had that. No more need for opiates or drugs that barely make a dent. https://en.m.wikipedia.org/wiki/Congenital_insensitivity_to_pain https://en.m.wikipedia.org/wiki/Congenital_insensitivity_to_...
- DrAwdeOccarim 5y ago
  It's coming very, very soon. Verve just IPO'ed and you check out their S1 to see their data on using the exact same idea (N1mΨ mRNA + gRNA inside LNP) to treat hypercholesterolemia! The data look amazing in non-human primates, which based on the Intellia data, suggest 10-fold lower dose in humans should work just fine. https://www.biospace.com/article/releases/verve-therapeutics-to-present-preclinical-data-from-gene-editing-programs-for-the-treatment-of-atherosclerotic-cardiovascular-disease-at-asgct/ https://www.biospace.com/article/releases/verve-therapeutics...
  - iandanforth 5y ago
    That's amazing! How does one register as a potential patient for the trials?
    - DrAwdeOccarim 5y ago
      www.clinicaltrials.gov once their IND is open, you'll be able to find it there! My guess is it's a year or so away before they start recruiting.
myko 5y ago
I'm very hopeful that someday these techniques will cure diseases like Huntington's
TaupeRanger 5y ago
Wow...this is a really big deal. Congratulations to this team and to the patients who were treated. I hope the treatment continues to keep the disease at bay.
DantesKite 5y ago
A lot of times you hear about these breakthroughs in medical papers or in mice, but this really feels different. Like an actual breakthrough with an actual cure for a specific disease. It's remarkable. Here's to more cures. God bless.
Waterluvian 5y ago
Turning medical science from a technical problem into an ethical one would be a massive epoch boundary for humanity, I’d say. More so than the Internet.
dcwardell 5y ago
Crazy genetics ideas I would like explored A modified tree that drops nuts of (nearly) pure graphite or some other form of nondecomposable carbon which we can easily harvest and sequester. Photosynthesis in humans to supplement our energy consumption. Shoutout to Knights of Sidonia. I understand the ethical issues surrounding the second one.
- kaba0 5y ago
  > A modified tree that drops nuts of (nearly) pure Well, we sort of have that in the form of specifically engineering bacteria to create some drugs, notably insulin. Though I’m sure graphene require additional biological structure and that is a much harder problem them adding/removing a few genes.
- semi-extrinsic 5y ago
  I believe the graphite nut proposal is too inefficient to work. A single large tree absorbs around 30 kg of CO2 per year. If it was able to put 10% of that into graphite nuts (which would be a very good efficiency), you end up with 0.8 kg of graphite nuts per tree per year. To match the IEAs projections for carbon capture (7.5 gigatonnes CO2 captured per year in 2050) you would need around 3*10^12 trees. That's about the same as the total number of trees in the world. So you need to replace all of the worlds trees, with the corresponding destruction of many of the biggest ecosystems on earth.
  - pkdpic_y9k 5y ago
    Thats a pretty solid breakdown, but that 3x10^12 was a little more hope-inspiring than I was expecting. Seems like a workable part of a larger multi-pronged solution if you streamlined the plants metabolism (?). Then again I dont know what in the h*ll Im talking about so theres that...
- onlyrealcuzzo 5y ago
  As someone who knows next to nothing about genetics, it's interesting to me that we haven't engineered a tree that grows faster than a hybrid poplar but thicker than a oak or sequoia (for carbon sequestration, and lumber). An added benefit would be if the wood after harvested lasted longer than a cedar. I'm guessing the reason this isn't possible is more due to the fact that it's just not financially worth the investment than it being too difficult. But I'd love to hear from someone who knows more about this stuff.
jonplackett 5y ago
Wonder how long it will be until this is used to enhance rather than just to cure. Eg selective fast twitch / slow twitch muscle fibres.
- rorykoehler 5y ago
  Probably already happening
  - jonplackett 5y ago
    Presumably it would be damn hard to detect if it was!
    - rorykoehler 5y ago
      Usain Bolt would be my number 1 candidate. His meteoric rise lines up perfectly date wise with the emergence of this technology and it is well documented that athletes have been using themselves as guinea pigs for various pre-commercial drugs due to the ability to avoid positive tests.
- jz_ 5y ago
  Something like this? https://www.studyfinds.org/superhero-vaccine-olympic-dna-euan-ashley/ https://www.studyfinds.org/superhero-vaccine-olympic-dna-eua...
  - jonplackett 5y ago
    Haha. What could possibly go wrong?
bawana 5y ago
So the religious right decided that we do not own our bodies, god does. Just as software companies issue a EULA, all children born since 2032 are required to have their parents sign a EULA. Genetic modification is strictly prohibited and punishable by reduction of the government stipend that everyone receives in fedcoin every month. Underground genetic modification labs are run by organized crime but unfortunately those using these labs also get an unplanned genetic modification in addition to the one they want. They are made dependent on a drug that only those labs can provide, for a price. In addition, there are monthly vaccination programs for citizens to protect them against genetic terrorists, carriers of lethal protoviruses who are engineered to carry and disseminate Covid derivatives that target HLA SUBTYPES common in Northern European and South American genotypes. Yes genetic modification is another wonderful technology that humans will weaponize….like atomic energy, like the internet…
janikvonrotz 5y ago
Not reading the entire article - I believe this is going the wrong way…
okareaman 5y ago
We have tried every imaginable remedy. In some instances there has been brief recovery, followed always by a still worse relapse. Physicians who are familiar with alcoholism agree there is no such thing as making a normal drinker out of an alcoholic. Science may one day accomplish this, but it hasn't done so yet. -- Alcoholics Anonymous Chapter 3, More About Alcoholism I may soon be able to drink again after having my genes edited, but I'm not sure I would do it
- bottled_poe 5y ago
  The word “always” in this passage doesn’t sound very scientific. Makes me wonder if the rest of the content has the same tone.
  - okareaman 5y ago
    Yes it does have this tone. It's not science. It was written in 1935 by Bill Wilson, a former stock market speculator and salesman. It's designed to be inspirational, as in, you may think you are a hopeless drunk, but I have a solution for you right here in this book. Give it a try. Edit: Something not often discussed is that Bill Wilson was hoping to make money from this book, being dead broke in the middle of the Great Depression. The first people he helped sober up convinced him that he had to give it away freely.
WheelsAtLarge 5y ago
It's only a matter of time before we use this to cosmetically modify our bodies. I predict that at the very least we'll use this technic to change our hair color and eye color. I will even say skin color too, with-in the next 50 years. Most people won't use it but there will be an active market , legal or illegal, for the modifications. The Sci-Fi future is here.
- pm90 5y ago
  On the contrary, I think most people will use it and those that don’t will likely do so out of religious reasons. This is really great. Being born into the wrong set of genes seems like an incredibly silly thing to restrict humans to. Allowing humans to choose their appearance seems like it could resolve a bunch of psycho social issues and hopefully people can live more happy lives (although I am aware that these things often lead to as yet unknown problems of their own…)
  - jtbayly 5y ago
    You... might want to read the story of the Sneeches by Dr. Seuss.
- TulliusCicero 5y ago
  Hair and eye color is bare minimum. You're gonna see cat girls and wolf boys and dragonkin and all kinds of weird ass shit. People making themselves intentionally disabled, people giving themselves a third arm, the sky's the limit!
MichaelMoser123 5y ago
Wikipedia says that they first used viruses as delivery agents; now it's nanoparticles, aparently to avoid destruction by the immune system. Also interesting that CRISPR gene editing was also the subject of a patent war. Amazing stuff... (also it took them less than a year to adopt the nanoparticle trick to CRISPR gene editing. Things are moving fast) https://en.wikipedia.org/wiki/CRISPR_gene_editing https://en.wikipedia.org/wiki/CRISPR_gene_editing https://news.harvard.edu/gazette/story/2020/11/coated-nanoparticles-survive-immune-system-and-deliver-drugs/ https://news.harvard.edu/gazette/story/2020/11/coated-nanopa...
- Alkhwarizmi 5y ago
  The patent war is already a settled matter for the reasonable folks amongst us, nevertheless there are people among us who still believe that the criminals at Harvard have any stake in this patent!
- MichaelMoser123 5y ago
  here is a better link: https://www.sciencemag.org/news/2021/06/crispr-injected-blood-treats-genetic-disease-first-time https://www.sciencemag.org/news/2021/06/crispr-injected-bloo... they say that they are using lipid nanoparticles, that's the same stuff that is used in the Moderna and Phizer covid vaccines. https://www.sciencedirect.com/science/article/pii/S0378517321003914 https://www.sciencedirect.com/science/article/pii/S037851732... We are living in the twenty first century...
imvetri 5y ago
Want to try chameleon color changing dna to pomerian dog
fighterpilot 5y ago
Stupid question: If he were to have kids, would they inherit this fix?
- Metacelsus 5y ago
  No. Sperm would not be edited by this method.
Bombthecat 5y ago
Could we hack our genes to need less oxygen and eat less? That could be useful in the future.
mrfusion 5y ago
Can anyone explain how this survives being in the blood stream and then how it actually gets into the nucleus of the cell?
- pas 5y ago
  Very similar to how a virion (virus particle) and its "payload". Here a lipid nanoparticle coats the genetic material. The exact chemistry used is highly selective to liver cells (so most of the particles will end up fusing with a liver cell), then inside the cell some enzyme or similar but more complicated molecular machinery (these usually have names ending in -ase, like protease, nuclease) unwraps it. Then it has special markers which signal that it needs transport to the nucleus. See NLS [0]. There CRISPR does its magic. The guide is the genetic pattern matcher. The big limitation is the length of this guide. The longer it is the safer it can be. [0] https://www.researchgate.net/post/How-does-the-CRISPR-guideRNA-get-into-the-Nucleus https://www.researchgate.net/post/How-does-the-CRISPR-guideR...
victor106 5y ago
This is just mind blowing. What are some good investment opportunities if you think this is going to revolutionize the world in the next 30-50 years?
- archon810 5y ago
  From another comment here, Verve? https://finance.yahoo.com/quote/VERV https://finance.yahoo.com/quote/VERV Any more suggestions?

600 points by hassanahmad 5y ago

Off topic: are there any central repositories tracking gene therapy progress for various genetic conditions, with a similar UX to Moderna’s mRNA pipeline tracker? https://www.modernatx.com/pipeline https://www.modernatx.com/pipeline

t3po7re5 5y ago
All FDA trials are listed here: https://clinicaltrials.gov/ https://clinicaltrials.gov/, I believe you can search by gene. It's not as nice as the moderna pipeline though.
- DSingularity 5y ago
  Thanks for that!

Causality1 5y ago

I must be out of the loop. Last I heard trials with CRISPR were making not only the desired genetic changes but also dozens of others at random points in the genome. Did they solve that problem?

dsign 5y ago
Humans improve technology all the time, CRISPR gene editing would be no exception. Straight from Wikipedia: https://en.wikipedia.org/wiki/LEAPER_gene_editing https://en.wikipedia.org/wiki/LEAPER_gene_editing I bet a dip into the specialized papers will show a multitude of these techniques.

softwaredoug 5y ago

The period missing from the title makes this very hard to parse what is being said.

caymanjim 5y ago
Agreed. NPR never used to use clickbait titles like this ("He ..." is pure clickbait). It's sad to see them doing it regularly now. I imagine the latest generation of journalists grew up thinking this is normal. I know HN prefers original headlines, but I wish these would be edited down when posted here.
- mjfl 5y ago
  "well then stop clicking on them!"
  - caymanjim 5y ago
    I often say the same thing myself. I expect it on CNN, and I do passively protest by ignoring links like this most of the time. NPR usually has good articles behind the links, and I'm more inclined to hold my nose and click if they make it to HN. In this case, the actual article is good. I'm lamenting the negative trend.

hmmmhmmmhmmm 5y ago

Original paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2107454?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2107454?query=fe... This is the first published IV-administration of a gene-editing CRISPR payload. Interesting convergence with the nanoparticles used in mRNA vaccines. Sickle-cell and immune reprogramming edits have been made on cells removed from the body. Josiah Zayner infamously injected himself with CRISPR at a conference years back, but (1) unpublished, AFAIK and (2) he had been drinking which likely attenuated the payload [and (3) he wanted bigger muscles, not to treat a disease]

gwern 5y ago
Mirror: https://www.gwern.net/docs/genetics/editing/2021-gillmore.pdf https://www.gwern.net/docs/genetics/editing/2021-gillmore.pd...

DrAwdeOccarim 5y ago

Wow, it worked...This uses LNPs similar to the recent Moderna and BioNTech/Pfizer vaccines, and N1m-pseudouridine mRNA, just like the mRNA vaccines. This is incredible.

changoplatanero 5y ago

Reminds me of this guy that cured himself of lactose intolerance. https://www.popularmechanics.com/science/health/a17804128/scientist-painstakingly-documents-his-own-diy-gene-therapy/ https://www.popularmechanics.com/science/health/a17804128/sc...

stuntkite 5y ago
His YouTube channel The Thought Emporium, is amazing. He just moved into a new lab and I really appreciate what he’s working on and how he communicates it. The robot painting fluorescent proteins is neat and recently he dropped a video demonstrating his adventures making synthetic opal. Apparently the edit made him totally lactose tolerant for over a year and now he has very mild lactose intolerance. He says he hasn’t redosed because he wants to improve the plasmid (I think that’s the right term, BUGFIX probably isn’t right) before he takes another run at it. Here’s his update video from last year on that endeavor. https://www.youtube.com/watch?v=aoczYXJeMY4 https://www.youtube.com/watch?v=aoczYXJeMY4
- faitswulff 5y ago
  Technically a plasmid is kind of like a software patch, but generally they're employed by bacteria and not eukaryotes like humans.
  - stuntkite 5y ago
    Interesting. I have watched nearly all of The Thought Emporium’s videos (so clearly I’m an expert, lol) and I think he uses the term plasmid to describe DNA he’s working on in the crazy bio IDE he uses. I think in this instance he applied it to a yeast that he cultured and put into pills and swallowed. He really is doing some neat stuff though. He’s inspired me to do some small bio hacking experiments and it ALMOST makes me want to go back to college.
    - shpongled 5y ago
      Plasmid is the correct term!

xwdv 5y ago

What are the limits of gene editing?

xf1cf 5y ago
A better question might be what are the ethical limits of gene editing. How long until we stumble over eugenics but with extra steps? It seems to me at least to be the natural conclusion of advanced gene editing. Law of unintended consequences and all that.
stuntkite 5y ago
I don’t think there are any aside from money, time, and experience. If you’d like to give yourself glowing purple eyes, huge muscles, and make it so you fart clouds of illegal street drugs you can but it’s much more difficult and messy than deleting ‘node_modules’, rebuilding, and doing a `git push —force` into prod at 5PM on a Friday before you take a long weekend.
wizzwizz4 5y ago
We're constrained by the subset of physics that can be implemented by proteins. Plus, the genetic code can't be too big, or it won't fit, but I doubt we'll ever hit that limit (provided we don't go the software route and build a giant tower of massive abstractions that gets copied everywhere).
- hoseja 5y ago
  Proteins and things built by proteins. Teeth aren't very protein-y.
  - xwdv 5y ago
    Why can’t we hardwire genes to continue growing teeth?
    - hoseja 5y ago
      Because we have specialized diverse teeth. Of course it's possible but that would be novel genetic programming which we just can't do.

DudeInBasement 5y ago

Cool, we can only show stories where it worked

carbocation 5y ago
Human clinical trials are pre-registered, in order to prevent exactly what you are describing (the 'file drawer problem').
- DudeInBasement 5y ago
  Not in all countries, just ask CCP
wesleywt 5y ago
Coming from a genetics background, I can tell you the fact that it worked once is a massive achievement in itself. This is science fiction.

zz865 5y ago

Would CRISPR be the technology people would use to modify a bat virus to make it human transmissable? This stuff should stay in its box.

kyriakos 5y ago
Knives can kill and save people. Almost anything can be used for bad purposes in the wrong hands.
- newsbinator 5y ago
  Not that I agree we should bury our heads in the sand like luddites, but to be fair to OP, knives can only hurt or help in a tiny human radius. It's hard to make an extinction-level weapon (or extension level accident) out of them. Being able to edit genes at will is a different story.
  - wizzwizz4 5y ago
    Viruses are an extinction-level weapon. CRISPR? Not so much. (And neither are likely to result in an extinction-level accident; you'd have to deliberately deploy potent bioweapons in multiple places to extinct us.)
    - deleted 5y ago
      [deleted]
    - SavantIdiot 5y ago
      Yes but the CRISPR engine is passed on to offspring which raises massive ethical questions. As I understand it (and hopefully I'm not way off base here) there is a technique that creates a "gene drive" which is kinda like an SDK that is inserted into the patients genome which improves the efficacy of CRISPR. This code finds its way into the gametes which is then passed on to children. The children did not ask for this SDK, but now they have it and it potentially becomes immortal in human DNA. On the one hand, cool: the SDK is there and possibly makes it even easier to alter DNA> On the other hand, holy shit: there's a ticking timebomb in the populations DNA now. It's called CRISPR-cas9: https://wyss.harvard.edu/media-post/crispr-cas9-gene-drives/ https://wyss.harvard.edu/media-post/crispr-cas9-gene-drives/ https://scicomm2020.wordpress.com/2020/02/24/controversial-gene-drive-system-found-to-fight-antibiotic-resistance/ https://scicomm2020.wordpress.com/2020/02/24/controversial-g...

calrueb 5y ago

The fact that we can apply these sort of therapies to an adult human who consists of millions upon millions of cells blows my mind. Having the ability to fix our "buggy" genetic code while we are alive is amazing.

hhjinks 5y ago
You're off by a _couple_ orders of magnitude. There are trillions of cells in a human body.
- hoseja 5y ago
  10^6 * 10^6 = 10^12
correcthorse123 5y ago
I think targetting tbe liver is far easier than most other tissues though, unfortunately.
- dclowd9901 5y ago
  Gotta start somewhere...
rorykoehler 5y ago
Monkey patching in production.

BurningFrog 5y ago

So this is editing liver cells, which I read somewhere is the easiest to do, since the liver absorbs foreign elements from the bloodstream. The success of this should mean that many genetic liver conditions can soon be treated this way. For other organs, I expect a longer wait.

codeulike 5y ago
The brain is particularly hard due to blood/brain barrier, crispr is too big a molecule to go through. So might need injections into cerebral spinal fluid for that
wgolsen 5y ago
The lung epithelium has also recently been transfected in humans (see Translate Bio cf drug; this and similar vehicles can deliver editing tools)

foreigner 5y ago

This is awesome but I'm curious why they tried it first on this super-rare disease instead of something more common?

inglor_cz 5y ago
My 2 cents: a) need to edit liver cells only, not the entire organism, b) the disease is deadly, so the patients do not have much to lose if anything goes wrong.
Turing_Machine 5y ago
Wild guess: it's because he's 65. Many of these severe genetic diseases kill their victims at relatively young ages. Ethical researchers are thus far being super-cautious about modifying the genome of someone who's likely to have children. While the article doesn't say, I wouldn't be surprised to learn that he has explicitly agreed not to have any (more?) children.
SoftwareMaven 5y ago
Extremely rare diseases and diseases that have no known treatment options are given more lax rules for testing. Without that, there would be no way to develop treatments for them, but it comes with a side benefit of providing a method to attempt new treatment modalities.

palijer 5y ago

I feel like I missed something, and now everywhere I look we have headlines like this. What's wrong with "CRISPR gene editing shown to cure Transthyretin amyloidosis in patient study" Maybe I'm now one of the old people who doesn't understand new usage of language. But I understand that usage dictates grammar rules, but I feel I missed something.

dogma1138 5y ago
NPR isn’t a research paper, or a researcher focused website.
eat_veggies 5y ago
The paper linked in the article is titled "CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis." That's close enough to your proposed title. If what you're looking for is a technical research paper meant for people intimately familiar with the field, then that's a great title. But it's a terrible title for an article meant for laypeople like us. The words "transthyretin amyloidosis" are utterly meaningless to me and most HN/NPR readers, but "He Inherited A Devastating Disease" tells me what kind of disease it is (devastating, heritable) and why CRISPR gene editing might be a big deal. It also helps clue me into the contents of the article. Because it is as much a summary of a key research result, as it is a profile of Patrick Doherty, a man affected by the disease. That's entirely missing from your title. None of this is new. "Write for your audience" is as old as writing itself.
ben_w 5y ago
I think it’s just an oddity of newspapers. Even before it was called “going viral”, they’ve been a bit like that.
phreack 5y ago
I know what you mean. These headlines read less like titles and more like lyrics in a song ("He was a skater boy. She said see you later boy."). It feels a bit condescending, as if it was aiming at children. I'd much prefer a title with a "person with thing does action" style.
boublepop 5y ago

ausbah 5y ago

>Doctors infused billions of microscopic structures known as nanoparticles carrying genetic instructions for the CRISPR gene-editor into four patients in London and two in New Zealand. The nanoparticles were absorbed by their livers, where they unleashed armies of CRISPR gene-editors. The CRISPR editor honed in on the target gene in the liver and sliced it, disabling production of the destructive protein. this is one of the coolest paragraphs I've read in a while. if it's accurate, serves as a great reminder that we're in the future as we speak

DoctorNick 5y ago
The record breaking temperatures that I'm suffering in the PNW right now serves as a grim reminder that we won't have much of a future, even with all this cool tech.
- cj 5y ago
  It’s not impossible to speculate the possibility that in 50-100 years, climate change could be reversed through a CRISPR-like technology (e.g. something that can be released and replicate in the environment, thereby changing it). Or at the very least, I can see a future where gene editing could relieve your suffering from heat by raising the threshold your body can tolerate :)
  - nr2x 5y ago
    At current rates of carbon outlay, there won’t be much of a world left to save in 100 years.
    - pkdpic_y9k 5y ago
      Not unless we all work our asses off! Engineers can do anything :^)
      - matmatmatmat 5y ago
        ... except politics, engineers are usually not very good at politics, and climate change is, in large part, a political problem.

iandanforth 5y ago

Please do familial hypercholesterolemia soon! I know it would be harder but getting started on targeting specific mutations could be fruitful. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681164/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681164/

bigmattystyles 5y ago
I want the CRISPR research that focuses on CIP accelerated. I have a minor chronic pain issue that will get worse over time (think sciatica). By the time I’m 60 in 25 years, it’d be great if we had that. No more need for opiates or drugs that barely make a dent. https://en.m.wikipedia.org/wiki/Congenital_insensitivity_to_pain https://en.m.wikipedia.org/wiki/Congenital_insensitivity_to_...
DrAwdeOccarim 5y ago
It's coming very, very soon. Verve just IPO'ed and you check out their S1 to see their data on using the exact same idea (N1mΨ mRNA + gRNA inside LNP) to treat hypercholesterolemia! The data look amazing in non-human primates, which based on the Intellia data, suggest 10-fold lower dose in humans should work just fine. https://www.biospace.com/article/releases/verve-therapeutics-to-present-preclinical-data-from-gene-editing-programs-for-the-treatment-of-atherosclerotic-cardiovascular-disease-at-asgct/ https://www.biospace.com/article/releases/verve-therapeutics...
- iandanforth 5y ago
  That's amazing! How does one register as a potential patient for the trials?
  - DrAwdeOccarim 5y ago
    www.clinicaltrials.gov once their IND is open, you'll be able to find it there! My guess is it's a year or so away before they start recruiting.

myko 5y ago

I'm very hopeful that someday these techniques will cure diseases like Huntington's

TaupeRanger 5y ago

Wow...this is a really big deal. Congratulations to this team and to the patients who were treated. I hope the treatment continues to keep the disease at bay.

DantesKite 5y ago

A lot of times you hear about these breakthroughs in medical papers or in mice, but this really feels different. Like an actual breakthrough with an actual cure for a specific disease. It's remarkable. Here's to more cures. God bless.

Waterluvian 5y ago

Turning medical science from a technical problem into an ethical one would be a massive epoch boundary for humanity, I’d say. More so than the Internet.

dcwardell 5y ago

Crazy genetics ideas I would like explored A modified tree that drops nuts of (nearly) pure graphite or some other form of nondecomposable carbon which we can easily harvest and sequester. Photosynthesis in humans to supplement our energy consumption. Shoutout to Knights of Sidonia. I understand the ethical issues surrounding the second one.

kaba0 5y ago
> A modified tree that drops nuts of (nearly) pure Well, we sort of have that in the form of specifically engineering bacteria to create some drugs, notably insulin. Though I’m sure graphene require additional biological structure and that is a much harder problem them adding/removing a few genes.
semi-extrinsic 5y ago
I believe the graphite nut proposal is too inefficient to work. A single large tree absorbs around 30 kg of CO2 per year. If it was able to put 10% of that into graphite nuts (which would be a very good efficiency), you end up with 0.8 kg of graphite nuts per tree per year. To match the IEAs projections for carbon capture (7.5 gigatonnes CO2 captured per year in 2050) you would need around 3*10^12 trees. That's about the same as the total number of trees in the world. So you need to replace all of the worlds trees, with the corresponding destruction of many of the biggest ecosystems on earth.
- pkdpic_y9k 5y ago
  Thats a pretty solid breakdown, but that 3x10^12 was a little more hope-inspiring than I was expecting. Seems like a workable part of a larger multi-pronged solution if you streamlined the plants metabolism (?). Then again I dont know what in the h*ll Im talking about so theres that...
onlyrealcuzzo 5y ago
As someone who knows next to nothing about genetics, it's interesting to me that we haven't engineered a tree that grows faster than a hybrid poplar but thicker than a oak or sequoia (for carbon sequestration, and lumber). An added benefit would be if the wood after harvested lasted longer than a cedar. I'm guessing the reason this isn't possible is more due to the fact that it's just not financially worth the investment than it being too difficult. But I'd love to hear from someone who knows more about this stuff.

jonplackett 5y ago

Wonder how long it will be until this is used to enhance rather than just to cure. Eg selective fast twitch / slow twitch muscle fibres.

rorykoehler 5y ago
Probably already happening
- jonplackett 5y ago
  Presumably it would be damn hard to detect if it was!
  - rorykoehler 5y ago
    Usain Bolt would be my number 1 candidate. His meteoric rise lines up perfectly date wise with the emergence of this technology and it is well documented that athletes have been using themselves as guinea pigs for various pre-commercial drugs due to the ability to avoid positive tests.
jz_ 5y ago
Something like this? https://www.studyfinds.org/superhero-vaccine-olympic-dna-euan-ashley/ https://www.studyfinds.org/superhero-vaccine-olympic-dna-eua...
- jonplackett 5y ago
  Haha. What could possibly go wrong?

bawana 5y ago

So the religious right decided that we do not own our bodies, god does. Just as software companies issue a EULA, all children born since 2032 are required to have their parents sign a EULA. Genetic modification is strictly prohibited and punishable by reduction of the government stipend that everyone receives in fedcoin every month. Underground genetic modification labs are run by organized crime but unfortunately those using these labs also get an unplanned genetic modification in addition to the one they want. They are made dependent on a drug that only those labs can provide, for a price. In addition, there are monthly vaccination programs for citizens to protect them against genetic terrorists, carriers of lethal protoviruses who are engineered to carry and disseminate Covid derivatives that target HLA SUBTYPES common in Northern European and South American genotypes. Yes genetic modification is another wonderful technology that humans will weaponize….like atomic energy, like the internet…

janikvonrotz 5y ago

Not reading the entire article - I believe this is going the wrong way…

okareaman 5y ago

We have tried every imaginable remedy. In some instances there has been brief recovery, followed always by a still worse relapse. Physicians who are familiar with alcoholism agree there is no such thing as making a normal drinker out of an alcoholic. Science may one day accomplish this, but it hasn't done so yet. -- Alcoholics Anonymous Chapter 3, More About Alcoholism I may soon be able to drink again after having my genes edited, but I'm not sure I would do it

bottled_poe 5y ago
The word “always” in this passage doesn’t sound very scientific. Makes me wonder if the rest of the content has the same tone.
- okareaman 5y ago
  Yes it does have this tone. It's not science. It was written in 1935 by Bill Wilson, a former stock market speculator and salesman. It's designed to be inspirational, as in, you may think you are a hopeless drunk, but I have a solution for you right here in this book. Give it a try. Edit: Something not often discussed is that Bill Wilson was hoping to make money from this book, being dead broke in the middle of the Great Depression. The first people he helped sober up convinced him that he had to give it away freely.

WheelsAtLarge 5y ago

It's only a matter of time before we use this to cosmetically modify our bodies. I predict that at the very least we'll use this technic to change our hair color and eye color. I will even say skin color too, with-in the next 50 years. Most people won't use it but there will be an active market , legal or illegal, for the modifications. The Sci-Fi future is here.

pm90 5y ago
On the contrary, I think most people will use it and those that don’t will likely do so out of religious reasons. This is really great. Being born into the wrong set of genes seems like an incredibly silly thing to restrict humans to. Allowing humans to choose their appearance seems like it could resolve a bunch of psycho social issues and hopefully people can live more happy lives (although I am aware that these things often lead to as yet unknown problems of their own…)
- jtbayly 5y ago
  You... might want to read the story of the Sneeches by Dr. Seuss.
TulliusCicero 5y ago
Hair and eye color is bare minimum. You're gonna see cat girls and wolf boys and dragonkin and all kinds of weird ass shit. People making themselves intentionally disabled, people giving themselves a third arm, the sky's the limit!

MichaelMoser123 5y ago

Wikipedia says that they first used viruses as delivery agents; now it's nanoparticles, aparently to avoid destruction by the immune system. Also interesting that CRISPR gene editing was also the subject of a patent war. Amazing stuff... (also it took them less than a year to adopt the nanoparticle trick to CRISPR gene editing. Things are moving fast) https://en.wikipedia.org/wiki/CRISPR_gene_editing https://en.wikipedia.org/wiki/CRISPR_gene_editing https://news.harvard.edu/gazette/story/2020/11/coated-nanoparticles-survive-immune-system-and-deliver-drugs/ https://news.harvard.edu/gazette/story/2020/11/coated-nanopa...

Alkhwarizmi 5y ago
The patent war is already a settled matter for the reasonable folks amongst us, nevertheless there are people among us who still believe that the criminals at Harvard have any stake in this patent!
MichaelMoser123 5y ago
here is a better link: https://www.sciencemag.org/news/2021/06/crispr-injected-blood-treats-genetic-disease-first-time https://www.sciencemag.org/news/2021/06/crispr-injected-bloo... they say that they are using lipid nanoparticles, that's the same stuff that is used in the Moderna and Phizer covid vaccines. https://www.sciencedirect.com/science/article/pii/S0378517321003914 https://www.sciencedirect.com/science/article/pii/S037851732... We are living in the twenty first century...

imvetri 5y ago

Want to try chameleon color changing dna to pomerian dog

fighterpilot 5y ago

Stupid question: If he were to have kids, would they inherit this fix?

Metacelsus 5y ago
No. Sperm would not be edited by this method.

Bombthecat 5y ago

Could we hack our genes to need less oxygen and eat less? That could be useful in the future.

mrfusion 5y ago

Can anyone explain how this survives being in the blood stream and then how it actually gets into the nucleus of the cell?

pas 5y ago
Very similar to how a virion (virus particle) and its "payload". Here a lipid nanoparticle coats the genetic material. The exact chemistry used is highly selective to liver cells (so most of the particles will end up fusing with a liver cell), then inside the cell some enzyme or similar but more complicated molecular machinery (these usually have names ending in -ase, like protease, nuclease) unwraps it. Then it has special markers which signal that it needs transport to the nucleus. See NLS [0]. There CRISPR does its magic. The guide is the genetic pattern matcher. The big limitation is the length of this guide. The longer it is the safer it can be. [0] https://www.researchgate.net/post/How-does-the-CRISPR-guideRNA-get-into-the-Nucleus https://www.researchgate.net/post/How-does-the-CRISPR-guideR...

victor106 5y ago

This is just mind blowing. What are some good investment opportunities if you think this is going to revolutionize the world in the next 30-50 years?

archon810 5y ago
From another comment here, Verve? https://finance.yahoo.com/quote/VERV https://finance.yahoo.com/quote/VERV Any more suggestions?