8 ms·

This stuff seems miraculous. > "Through minimally invasive surgery, Shu injected adeno-associated virus (AAV) engineered to carry and deliver functioning copie

by gota 2y ago

This stuff seems miraculous. > "Through minimally invasive surgery, Shu injected adeno-associated virus (AAV) engineered to carry and deliver functioning copies of the human OTOF transgene, into the children’s inner ears. " Can't read that and not get curious, excited, for the future. Congratulations to all those involved in the research and thanks to all who contributed to it - including all taxpayers if public funding was given, even indirectly (i.e. in the schooling and education, grants, for said researchers)

dyauspitr 2y ago
I can’t wait for a geneCAD where we for example, design wings for a human body and then it works out the rest and generates a CRISPR based AAV that you can inject yourself with. True race and sex changes too. Hopefully in the next 50 years but that’s wishful thinking.
- kevin_thibedeau 2y ago
  There are potential serious downsides if these inserted genes end up on a different chromosome than normal and become carried by gametes to offspring who may suffer from overexpression.
  - dyauspitr 2y ago
    I presume at the point we can generate CAD like designer gene modifications, overexpression would just be another problem that can be fixed by more modification.
    - Auracle 2y ago
      Eh, maybe you’ll run into the problem the Asgard had in Stargate. Too much editing over time = couldn’t procreate anymore. Little bugs add up.
      - ben_w 2y ago
        That was a plot device that didn't make sense to me: they could upload and download a functional copy of their brains (and also human brains), but they didn't keep a backup copy of their old DNA?
        Auracle 2y ago
        I agree, plus they at one point had a whole damn older preserved Asgard. That and how rushed they made their end of that particular story in the last episode made me hate it.
  - samstave 2y ago
    [dead]
- antegamisou 2y ago
  We need to keep away biotech OpenAI-wannabes apparently.
- mylons 2y ago
  it’s happening! i just finished something that assists in “CRISPR Design” and helps gene editors.
- nkrisc 2y ago
  Taking it seriously for a moment, that still seems outlandish even in a sci-fi scenario. The amount of changes that would be necessary to the body for a human to achieve autonomous powered flight would be substantial. Given our overall density, we would need enormous wings and musculature. Consider that the heaviest flying birds alive today weigh maybe 40lbs and have a wingspan of 8ft or so. If we naively extrapolate that linearly then an adult weighing 160lbs would need a 32ft wingspan. There were flying pterosaurs that weighed much more than the heaviest flying birds today, but they were also the size of small planes and it’s a bit of a debate how well they even flew. They may have struggled to even take flight. So injecting yourself with some designer DNA isn’t just going to make you grow wings, it would have to completely transform you into a completely different creature, simply due to the physics of flight. Additionally, you need not only to be able to fly, but your body needs to function well enough to stay in this new state. You would also likely need an enormous caloric intake to support the massive new growth, or it would take a very, very long time. It wouldn’t be designing wings for a human, it would be designing a be creature based on a human but not human at all, really. Call me shortsighted but I don’t really see how that will ever be possible.
  - dyauspitr 2y ago
    Your point seems to be that massive changes are required to achieve wings. I’m saying that’s not impossible and an acceptable modification to whoever wants to do this to themselves. As long as you can maintain the brain as is, I don’t see there being a problem with radically modifying the rest of the body. Argentavis magnificens had a wingspan of around 24ft and weighed around 72 kgs or a 160lbs which is close to what an average human weighs. If you compare growth rates to other mammals like elephants, I doubt a change like that would take much more than 5-10 years.
    - nkrisc 2y ago
      > As long as you can maintain the brain as is, That’s the question, can a human sized body that can fly additionally support a human sized brain? I suspect you would have to spend nearly every waking minute eating to support both. Or at least a substantial portion of your day. No time for hacking, gotta eat. You’ll probably have to pay full up front for this, as no one will finance you since you’ll be too busy foraging for sugary fruit or carrying livestock off to your eyrie to work a job to pay it back. Finally, this raises another question I won’t even attempt to answer: is it even possible for you to still be “you” in another body? How responsible is your body, beyond just your brain, responsible for making you who you are?
- taf2 2y ago
  That would be cool - maybe a simple 20/20 vision would be a great next step after hearing
- akoboldfrying 2y ago
  Let's try to fix the world's vast number of actual, boring health problems before trying to add the equivalent of spoilers and chrome-plated hubcaps to perfectly healthy human bodies.
  - dyauspitr 2y ago
    You can do both things at the same time.
    - akoboldfrying 2y ago
      That's true if we assume unlimited resources and equal awareness/perceived social value of the two applications. But I think the former doesn't hold, and the latter is greatly influenced by sites like HN, where I'm disappointed to consistently (if not exclusively) see breathless proposals for ways to design shinier hubcaps whenever some promising new technology appears. Yes, they can and likely will both happen to some extent, but I think they aren't independent, so I feel justified in trying to nudge the public conversation back towards the issues that I think matter more.
      - evilduck 2y ago
        Cosmetic surgery for vanity has helped improve the techniques and procedures and even the number of skilled practitioners that can then help those with disfigurements and deformities.
        JumpCrisscross 2y ago
        Hell, cancer treatment for pets has advanced human oncology [1]. Scientific discovery is rarely zero sum. [1] https://www.upstate.edu/whatsup/2019/0220-treatment-for-canine-cancer-serves-as-model-for-humans.php https://www.upstate.edu/whatsup/2019/0220-treatment-for-cani...
        _factor 2y ago
        And cigarettes have benefited the lung cancer research centers. Just because it works doesn’t make it the best course.
- narrator 2y ago
  No doubt you'll see an Android/Apple split and the Apple people won't be able to date the Android people because of incompatible augmented pheromones that smell funny if you're not on the same platform.
- _yb2s 2y ago
  Synthetic biology CAD software does exist, and works better than most people would expect, but of course are not at the level you are imagining yet.
  - Nesco 2y ago
    Could you provide some resources/links please?
    - _yb2s 2y ago
      It's hard to summarize because there are about a dozen different categories of things that could reasonably considered "biological CAD" and often would all be used together in a single synthetic biology project. For example: Retrobiosynthesis simulates biochemistry backwards, to find the steps necessary for a biological system to build something, usually a small molecule. Galaxy-SynBioCAD / Retropath would be one example: https://jfaulon.com/galaxy-synbiocad-portal/ https://jfaulon.com/galaxy-synbiocad-portal/ Constraint based metabolic modeling models cellular metabolism, and lets you simulate adding and removing chemical reactions to a cell, and predict the outcomes. COBRApy would be one example software tool: https://opencobra.github.io/cobrapy/ https://opencobra.github.io/cobrapy/ Design editors for DNA plasmids, like the Teselagen design editor let you construct DNA sequences representing new biological capabilities to be added to an engineered cell, which can then be synthesized or constructed. Teselagen design module: https://teselagen.com/design-module/ https://teselagen.com/design-module/ Generative AI systems can 'hallucinate' functional proteins and DNA sequences that meet a design specification for function and/or shape. For example, GenerateBio's Chroma model can literally take a 3D file designed in a standard CAD program, and then automatically come up with an amino acid sequence that will fold into a protein with that exact 3D shape- and it actually works. https://github.com/generatebio/chroma https://github.com/generatebio/chroma An emerging field is coupling all of these types of tools with predictive models to enable 'inverse design' where you create a spec of what you want, such as a material with some desired properties, and it will automatically suggest biological routes to it.
- inglor_cz 2y ago
  Our bodies are very much not suitable for flight. Birds look differently from the inside. It might prove easier to grow biological pylons for external jet engines...
- hinkley 2y ago
  Dan Simmons, Hyperion Cantos. “Biosculpting”
- TyrianPurple 2y ago
  Excuse me, are you The Qu?
m3kw9 2y ago
I thought you can’t just inject genes and then the body will start replicate it. Does it need periodic injections?
- rguiscard 2y ago
  That is why the gene is put into a harmless virus which will injects the gene into cells. It takes advantage of what virus usually does.
- toufka 2y ago
  If the DNA is in the cell's nucleus, the DNA will be utilized to produce whatever gene is encoded in the DNA. But if the DNA is just floating around on its own it will not survive a cell division event and the material would need to be periodically reinjected to keep working. However, if the injected DNA is part of a full chromosome, it will be replicated when the cell divides - and will be permanent as long as the cell or its progeny survive. Some viruses will just inject the DNA into cells, but will not become part of the cell's genome ("transient" transduction). Other viruses (like lentiviruses and these adeno-associated viruses [AAVs]) inject their DNA not just into the cells, but also have machinery that splices their payload DNA directly into the cell's chromosomes ("integrated"). The location in the genome of the splicing event is relatively random. Random is not necessarily great as it could interrupt other genes already in the chromosome. CRISPR is a now-famous tool that helps "integrate" DNA into a specific spot in the genome by being guided to a specific location with a small piece of a specific sequence. Once the DNA is integrated, any cell, and any of the cell's progeny, will produce or "express" the gene on the delivered DNA. In this case, they delivered the 5991 characters of DNA associated with the OROF gene [1]. [1] https://en.wikipedia.org/wiki/Otoferlin https://en.wikipedia.org/wiki/Otoferlin
  - rekttrader 2y ago
    Thank you for this description of how it works. It seems like truly beautiful and terrifying magic.
  - bglazer 2y ago
    This is actually not totally correct. AAV’s form episomes, which are circular DNA structures that are basically extra chromosomes. The fact that AAV’s don’t randomly insert themselves into DNA makes them safer for clinical uses like this. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519600/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519600/
tim333 2y ago
I'm sure there will be other treatments based on AAV and CRISPR. I'm interested in ALS as a relative has it and that stuff is one of the only approaches that might work. The had a go on mice with so so results - lived longer but no cure https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30011-3 https://www.cell.com/molecular-therapy-family/molecular-ther...

by gota 2y ago

dyauspitr 2y ago

I can’t wait for a geneCAD where we for example, design wings for a human body and then it works out the rest and generates a CRISPR based AAV that you can inject yourself with. True race and sex changes too. Hopefully in the next 50 years but that’s wishful thinking.

kevin_thibedeau 2y ago
There are potential serious downsides if these inserted genes end up on a different chromosome than normal and become carried by gametes to offspring who may suffer from overexpression.
- dyauspitr 2y ago
  I presume at the point we can generate CAD like designer gene modifications, overexpression would just be another problem that can be fixed by more modification.
  - Auracle 2y ago
    Eh, maybe you’ll run into the problem the Asgard had in Stargate. Too much editing over time = couldn’t procreate anymore. Little bugs add up.
    - ben_w 2y ago
      That was a plot device that didn't make sense to me: they could upload and download a functional copy of their brains (and also human brains), but they didn't keep a backup copy of their old DNA?
      - Auracle 2y ago
        I agree, plus they at one point had a whole damn older preserved Asgard. That and how rushed they made their end of that particular story in the last episode made me hate it.
- samstave 2y ago
  [dead]
antegamisou 2y ago
We need to keep away biotech OpenAI-wannabes apparently.
mylons 2y ago
it’s happening! i just finished something that assists in “CRISPR Design” and helps gene editors.
nkrisc 2y ago
Taking it seriously for a moment, that still seems outlandish even in a sci-fi scenario. The amount of changes that would be necessary to the body for a human to achieve autonomous powered flight would be substantial. Given our overall density, we would need enormous wings and musculature. Consider that the heaviest flying birds alive today weigh maybe 40lbs and have a wingspan of 8ft or so. If we naively extrapolate that linearly then an adult weighing 160lbs would need a 32ft wingspan. There were flying pterosaurs that weighed much more than the heaviest flying birds today, but they were also the size of small planes and it’s a bit of a debate how well they even flew. They may have struggled to even take flight. So injecting yourself with some designer DNA isn’t just going to make you grow wings, it would have to completely transform you into a completely different creature, simply due to the physics of flight. Additionally, you need not only to be able to fly, but your body needs to function well enough to stay in this new state. You would also likely need an enormous caloric intake to support the massive new growth, or it would take a very, very long time. It wouldn’t be designing wings for a human, it would be designing a be creature based on a human but not human at all, really. Call me shortsighted but I don’t really see how that will ever be possible.
- dyauspitr 2y ago
  Your point seems to be that massive changes are required to achieve wings. I’m saying that’s not impossible and an acceptable modification to whoever wants to do this to themselves. As long as you can maintain the brain as is, I don’t see there being a problem with radically modifying the rest of the body. Argentavis magnificens had a wingspan of around 24ft and weighed around 72 kgs or a 160lbs which is close to what an average human weighs. If you compare growth rates to other mammals like elephants, I doubt a change like that would take much more than 5-10 years.
  - nkrisc 2y ago
    > As long as you can maintain the brain as is, That’s the question, can a human sized body that can fly additionally support a human sized brain? I suspect you would have to spend nearly every waking minute eating to support both. Or at least a substantial portion of your day. No time for hacking, gotta eat. You’ll probably have to pay full up front for this, as no one will finance you since you’ll be too busy foraging for sugary fruit or carrying livestock off to your eyrie to work a job to pay it back. Finally, this raises another question I won’t even attempt to answer: is it even possible for you to still be “you” in another body? How responsible is your body, beyond just your brain, responsible for making you who you are?
taf2 2y ago
That would be cool - maybe a simple 20/20 vision would be a great next step after hearing
akoboldfrying 2y ago
Let's try to fix the world's vast number of actual, boring health problems before trying to add the equivalent of spoilers and chrome-plated hubcaps to perfectly healthy human bodies.
- dyauspitr 2y ago
  You can do both things at the same time.
  - akoboldfrying 2y ago
    That's true if we assume unlimited resources and equal awareness/perceived social value of the two applications. But I think the former doesn't hold, and the latter is greatly influenced by sites like HN, where I'm disappointed to consistently (if not exclusively) see breathless proposals for ways to design shinier hubcaps whenever some promising new technology appears. Yes, they can and likely will both happen to some extent, but I think they aren't independent, so I feel justified in trying to nudge the public conversation back towards the issues that I think matter more.
    - evilduck 2y ago
      Cosmetic surgery for vanity has helped improve the techniques and procedures and even the number of skilled practitioners that can then help those with disfigurements and deformities.
      - JumpCrisscross 2y ago
        Hell, cancer treatment for pets has advanced human oncology [1]. Scientific discovery is rarely zero sum. [1] https://www.upstate.edu/whatsup/2019/0220-treatment-for-canine-cancer-serves-as-model-for-humans.php https://www.upstate.edu/whatsup/2019/0220-treatment-for-cani...
      - _factor 2y ago
        And cigarettes have benefited the lung cancer research centers. Just because it works doesn’t make it the best course.
narrator 2y ago
No doubt you'll see an Android/Apple split and the Apple people won't be able to date the Android people because of incompatible augmented pheromones that smell funny if you're not on the same platform.
_yb2s 2y ago
Synthetic biology CAD software does exist, and works better than most people would expect, but of course are not at the level you are imagining yet.
- Nesco 2y ago
  Could you provide some resources/links please?
  - _yb2s 2y ago
    It's hard to summarize because there are about a dozen different categories of things that could reasonably considered "biological CAD" and often would all be used together in a single synthetic biology project. For example: Retrobiosynthesis simulates biochemistry backwards, to find the steps necessary for a biological system to build something, usually a small molecule. Galaxy-SynBioCAD / Retropath would be one example: https://jfaulon.com/galaxy-synbiocad-portal/ https://jfaulon.com/galaxy-synbiocad-portal/ Constraint based metabolic modeling models cellular metabolism, and lets you simulate adding and removing chemical reactions to a cell, and predict the outcomes. COBRApy would be one example software tool: https://opencobra.github.io/cobrapy/ https://opencobra.github.io/cobrapy/ Design editors for DNA plasmids, like the Teselagen design editor let you construct DNA sequences representing new biological capabilities to be added to an engineered cell, which can then be synthesized or constructed. Teselagen design module: https://teselagen.com/design-module/ https://teselagen.com/design-module/ Generative AI systems can 'hallucinate' functional proteins and DNA sequences that meet a design specification for function and/or shape. For example, GenerateBio's Chroma model can literally take a 3D file designed in a standard CAD program, and then automatically come up with an amino acid sequence that will fold into a protein with that exact 3D shape- and it actually works. https://github.com/generatebio/chroma https://github.com/generatebio/chroma An emerging field is coupling all of these types of tools with predictive models to enable 'inverse design' where you create a spec of what you want, such as a material with some desired properties, and it will automatically suggest biological routes to it.
inglor_cz 2y ago
Our bodies are very much not suitable for flight. Birds look differently from the inside. It might prove easier to grow biological pylons for external jet engines...
hinkley 2y ago
Dan Simmons, Hyperion Cantos. “Biosculpting”
TyrianPurple 2y ago
Excuse me, are you The Qu?

m3kw9 2y ago

I thought you can’t just inject genes and then the body will start replicate it. Does it need periodic injections?

rguiscard 2y ago
That is why the gene is put into a harmless virus which will injects the gene into cells. It takes advantage of what virus usually does.
toufka 2y ago
If the DNA is in the cell's nucleus, the DNA will be utilized to produce whatever gene is encoded in the DNA. But if the DNA is just floating around on its own it will not survive a cell division event and the material would need to be periodically reinjected to keep working. However, if the injected DNA is part of a full chromosome, it will be replicated when the cell divides - and will be permanent as long as the cell or its progeny survive. Some viruses will just inject the DNA into cells, but will not become part of the cell's genome ("transient" transduction). Other viruses (like lentiviruses and these adeno-associated viruses [AAVs]) inject their DNA not just into the cells, but also have machinery that splices their payload DNA directly into the cell's chromosomes ("integrated"). The location in the genome of the splicing event is relatively random. Random is not necessarily great as it could interrupt other genes already in the chromosome. CRISPR is a now-famous tool that helps "integrate" DNA into a specific spot in the genome by being guided to a specific location with a small piece of a specific sequence. Once the DNA is integrated, any cell, and any of the cell's progeny, will produce or "express" the gene on the delivered DNA. In this case, they delivered the 5991 characters of DNA associated with the OROF gene [1]. [1] https://en.wikipedia.org/wiki/Otoferlin https://en.wikipedia.org/wiki/Otoferlin
- rekttrader 2y ago
  Thank you for this description of how it works. It seems like truly beautiful and terrifying magic.
- bglazer 2y ago
  This is actually not totally correct. AAV’s form episomes, which are circular DNA structures that are basically extra chromosomes. The fact that AAV’s don’t randomly insert themselves into DNA makes them safer for clinical uses like this. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519600/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519600/

tim333 2y ago

I'm sure there will be other treatments based on AAV and CRISPR. I'm interested in ALS as a relative has it and that stuff is one of the only approaches that might work. The had a go on mice with so so results - lived longer but no cure https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30011-3 https://www.cell.com/molecular-therapy-family/molecular-ther...