[HN Gopher] CRISPR-like tools that finally can edit mitochondria...
       ___________________________________________________________________
        
       CRISPR-like tools that finally can edit mitochondria DNA
        
       Author : ck2
       Score  : 138 points
       Date   : 2025-10-14 13:21 UTC (9 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | Miaourt wrote:
       | A nice soul have a non-paywalled version to share ?
        
         | byrantech wrote:
         | https://www.nature.com/articles/d41586-025-03307-x.pdf
         | 
         | this should work?
        
           | Miaourt wrote:
           | Maybe I'm just stupid, but I'm seeing the typical "fade-out"
           | at the bottom of the article, followed by a subscription-
           | wall, suggesting more of the content is behind this gate.
           | Tho, maybe the "Making the edit" infographic is really the
           | bottom of the article...
        
             | bil7 wrote:
             | the only current archive on archive.is also has that. Watch
             | this space for a complete archive, hopefully:
             | 
             | https://archive.is/https://www.nature.com/articles/d41586-0
             | 2...
        
       | varispeed wrote:
       | Imagine the future - vibe coding own DNA.
       | 
       | "Hey ChatGPT, I need third ear. Make it grow in two months."
        
         | Iolaum wrote:
         | Now we "just" need a CRISPR-MCP server :p
        
           | mountainriver wrote:
           | On the public internet
        
         | CSMastermind wrote:
         | I've been reading a lot about biochemistry lately and it's
         | actually insane how complicated all of life is. The idea that
         | we can edit genes at all is a miracle and I think most software
         | engineers significantly underestimate how hard it would be to
         | make meaningful changes to our bodies through gene editing.
        
           | lanfeust6 wrote:
           | Recently have been reading the Gene by Mukherjee. I'm amazed
           | at what had been accomplished in the mid 20th Century. A lot
           | of what still seems crazy now was done already albeit in
           | small scale.
        
           | fragmede wrote:
           | Growing new appendages is clearly much more involved, but a
           | Youtuber was able to give themselves lactose tolerance for a
           | couple of months (they were lactose intolerant before).
           | Assuming it wasn't faked for views, and that we are what we
           | eat, that suggests other modifications to gut bateria aren't
           | inconceivably far off.
        
             | throwup238 wrote:
             | Considering that there aren't any mammals that can regrow
             | appendages, chances are adding an appendage would be
             | impossible with gene editing because it would require
             | editing both the mother and offspring to support novel
             | embryonic development.
        
               | clort wrote:
               | I seem to think that human children can regrow the tips
               | of their finger if it is cut off (I think the nail is ok,
               | not the joint) though I don't know where I learned that,
               | perhaps a first aid course. I've never tried it though.
        
               | throwup238 wrote:
               | That is correct, as long as the injury doesn't take out
               | the nail bed. That implies that there is some sort of
               | growth factor involved with the nail bed as a signaling
               | center, but regrown finger tips are a very simple case
               | compared to actual appendages.
               | 
               | Finger tips are mostly fatty soft tissue minus the
               | muscle, which is known to regenerate. Stuff like nerves
               | are a completely different issue and children who regrow
               | finger tips usually lose finer sensory input like two
               | point discrimination.
        
             | seanhunter wrote:
             | My understanding is that lactose tolerance is a
             | particularly interesting case because lactose _tolerance_
             | is in fact the mutation and lactose _intolerance_ is the
             | "default". It's just that for historical reasons lactose
             | tolerance obviously conferred an advantage in Europe in
             | particular which is why the mutation persisted. That's why
             | around 40% of the global population are lactose tolerant
             | and intolerance is the global norm.
             | 
             | https://en.wikipedia.org/wiki/Lactase_persistence
        
             | jryb wrote:
             | If we're thinking about the same youtuber, I found that
             | experimental design to be really poor. They said they were
             | lactose intolerant as a child, but they didn't confirm that
             | they still were (decades?) later. I was lactose intolerant
             | until I was six and then it just resolved on its own
             | (perhaps this wasn't even lactose intolerance but a
             | reaction to something associated with lactose).
             | 
             | What they should have done was eat a pizza before the
             | treatment, gotten sick, then taken the treatment and shown
             | that the same pizza had no effect afterwards.
        
           | toasterlovin wrote:
           | Unfortunately biology only does spaghetti code.
        
             | BartjeD wrote:
             | We just haven't found God's IDE yet
        
               | rabf wrote:
               | Maybe this: https://teselagen.com/
               | 
               | Nice list here: https://github.com/davidliwei/awesome-
               | CRISPR
        
               | psunavy03 wrote:
               | from primordial_chaos import Universe
               | 
               | # TODO: This is a complete hack that needs to be
               | refactored, but it works for now.
               | 
               | def quantum_physics() -> Universe:
        
             | testdelacc1 wrote:
             | I read a book about the immune system and it's actually
             | insane how much tech debt there is in there. We have
             | several systems, each one built a hundred million years
             | after the previous one. Each one targets the kind of
             | threats that were prevalent then but are still there
             | because they haven't completely disappeared. So much
             | complexity, and systems can go haywire so easily -
             | autoimmune diseases, allergic reactions and so on.
             | 
             | And yet, like a startup that found product market fit with
             | a garbage tech stack, this pile of jenga spaghetti is still
             | going strong. Complexity doesn't matter, people dying
             | because they looked at a peanut doesn't matter - ultimately
             | this spaghetti works well enough to get humans to where we
             | are today.
        
               | andy_ppp wrote:
               | Great comment, which book did you read?
        
             | themafia wrote:
             | It doesn't really. The START and STOP codons define clear
             | cut frames for your cells to use. Think of your DNA like
             | ECC memory. There's a bunch of extra stuff in there which
             | makes it suitable for use as a memory storage. It has
             | nothing to do with the actual replicated genes and their
             | associated proteins or the role of those within the body.
             | 
             | The really cool part about that storage is it is
             | environmentally sensitive. So as the environment changes
             | around your DNA it's shape slightly changes and so the
             | available START sites also change which alters the types
             | and numbers of genes that are copied for use.
             | 
             | Biology isn't one system it's dozens all stacked and
             | layered on top of each other. It's like trying to
             | understand computing by watching what individual electrons
             | do. Of course it looks messy. On the larger scale it's far
             | more elegant.
        
               | dekhn wrote:
               | start and stop codons are not as clear cut as you're
               | implying (there are often several start sites), and
               | variable splicing adds a bunch more stochasticity.
        
               | themafia wrote:
               | There are also 6 potential open reading frames in any
               | span of DNA. 3 phases and two directions. You're looking
               | at it backwards though. The fact that there are options
               | means the DNA can have the same meaning but a different
               | electrochemical signature. It's a structural memory. It's
               | both your genes and the necessary gradient to cause them
               | to arrange in your chromosomes correctly.
               | 
               | You call it stochastic. I call it scaffolding.
        
               | dekhn wrote:
               | What you're saying makes absolutely zero sense from a
               | modern DNA research perspective.
        
               | themafia wrote:
               | I'm not here to represent the modern DNA research
               | perspective. You seem to have adequate access to that
               | already. I'm a programmer. If that means you must
               | discount my point of view entirely then so be it.
        
           | zackmorris wrote:
           | I'm definitely outside my wheelhouse but I've been thinking
           | about this lately.
           | 
           | I heard that CRISPR can only cut segments that match a
           | pattern, so if there are other genes between the ends that
           | are cut, then those are lost as well. So to do a proper
           | substitution, we'd need to sequence the patient's genes
           | between the cuts, and possibly the whole rest of their
           | genome, to make sure that any patterns don't appear anywhere
           | else, so that nothing important is removed elsewhere.
           | 
           | That sounds insurmountable, but it may not be. Human beings
           | basically all have nearly identical DNA, so maybe we can just
           | derive someone's diff from a known DNA sample. If I ever won
           | the internet lottery, that's the sort of tool that I would
           | want to invest in.
           | 
           | Then we probably need more vectors to get CRISPR where it
           | needs to go. That sounds like more of an engineering
           | challenge to me than having to invent something new. Or at
           | least, the number of vectors found might correlate with R&D
           | funding.
           | 
           | It's not that hard for me to imagine getting the recipe
           | figured out to the point that it's 100% reliable and can even
           | be delivered to specific parts of the body with a certain
           | frequency of light, for example.
           | 
           | Then come up with an iterative process, probably using AI, to
           | catalog and repair all major genetic disorders.
           | 
           | I don't see too much mystery there, even if the final recipes
           | seem byzantine to human understanding. But I wanted to be a
           | genetic engineer before I got into computers when I was 12,
           | so I've had a long time to think about it. If AI eats the
           | programming world like it looks like it's going to, maybe we
           | can find work in biotech. Then it's probably 5-10 years
           | before gene editing is a solved problem.
        
         | thwarted wrote:
         | This reminded me of the 1995 The Outer Limits episode "The New
         | Breed".
        
         | tracker1 wrote:
         | I don't like to be alarmist, but some of this is a little
         | scary, IMO. Small changes in a society can have massive impacts
         | over generations. If you look at what happened to experiments
         | with feeding house cats an altered diet in just a few
         | generations. People are already eating a lot of things that
         | wouldn't even be considered food a couple centuries ago, and
         | maybe still shouldn't be.
         | 
         | We have a lot of increasing hormone production issues in
         | western society already, I'm not sure that fiddling with things
         | further is a real solution here without risking a lot of damage
         | to society as a whole.
        
           | lazyfanatic42 wrote:
           | The amount of change that has happened just because of The
           | Internet, and the speed of those changes is already too fast
           | for us to cope with. We haven't even properly coped with that
           | single change as a society and things are just
           | accelerating...
        
           | zafka wrote:
           | > If you look at what happened to experiments with feeding
           | house cats an altered diet in just a few generations.
           | 
           | Can you point to a reference?
        
             | tracker1 wrote:
             | https://drsurinderarora.com/articles/f/nutrition-for-
             | dentiti...
        
         | guluarte wrote:
         | "Hey you #$#@ remove the ear from my anus"
        
         | peder wrote:
         | And then when it gets it wrong and you ask why it grew a nose
         | instead of an ear: "You're absolutely right! I can fix this!"
        
           | echelon wrote:
           | You mean cancer.
           | 
           | Or a wicked disease state like Huntington's that causes your
           | DNA to slip.
           | 
           | Simple failures with catostrophic outcomes are much more
           | likely than rewiring and restarting all of the developmental
           | program across huge cell and tissue populations.
           | 
           | It would be more likely to grow transplant tissue
           | exogenously. It's far safer than using the body as a test
           | tube.
           | 
           | These gene editing techniques are used to fix simple
           | (typically one cause) genetic diseases. Not reengineer live
           | organisms "in flight".
        
             | hinkley wrote:
             | Your liver is covered with ears and they've started
             | spreading to your lymph nodes.
        
         | rolisz wrote:
         | Take a look at Michael Levin's work: he's been able to get
         | animals to grow eyes on their legs (or something similar),
         | without gene manipulation, but just by messing with
         | bioelectrical fields. Paper:
         | https://pmc.ncbi.nlm.nih.gov/articles/PMC3587383/?utm YouTube
         | interview: https://youtu.be/Kpx5isuKD1c?si=RU6fztq_RexUvYif
        
         | burnte wrote:
         | Two months go by then suddenly three more ears appear on your
         | head.
         | 
         | Damn those hallucinations!
        
       | koeng wrote:
       | We've known TALENs work for years. For example -
       | https://pmc.ncbi.nlm.nih.gov/articles/PMC4817924/ - from 2015
       | 
       | I worked on a project many years ago to do RNA import into yeast
       | mitochondria (and then hopefully reverse transcribe there).
       | Didn't work, and a lot of the info on RNA import into the
       | mitochondria is... suspect.
       | 
       | Mitochondria engineering is just actually tough. 30 years and no
       | new protocols for getting DNA in there :(
        
       ___________________________________________________________________
       (page generated 2025-10-14 23:01 UTC)