I was listening to a talk from a leading nanoparticle researcher. He basically said that making new nanoparticles and characterising them is great for writing papers but they all fail actual testing as therapeutic delivery devices. In oncology there are kinda only two nanoparticle therapies - Abraxane, which is a well known chemotherapy drug bound to albumin; liposomal doxorubicin, an encapsulated form of another well known chemotherapy drug. They have been around a while and they are not exactly game changing, extending survival a modest amount at best. Nanoparticles are overrated from where I sit, as are University press releases.
On the other hand, antibody based therapies are amazing revolutionary drugs in oncology. Chief among them is Keytruda which has improved the lives of so many patients and has $2billion in sales every month and rising. Most recently, sticking chemotherapy drugs or radioisotopes on the end of antibodies (or smaller antibody like proteins) has shown great results as a delivery vehicle. Are these ‘nanoparticles’? No, just actual drugs that work.
Oncology is about treating tumors (aka cancer). Cystic fibrosis is a genetic disorder with a well-known mechanism, a defective channel in the cell membrane.
It's already well established that improving the function of the CFTR or increasing the number of them is effective in mitigating the seriousness of the condition.
I hate all the buzzwords around "nanoparticles", but here we're talking about "nanoparticle" encapsulated mRNA-- like is used in the mRNA-based COVID vaccines.
Here, the formulation is intended for inhalation instead of injection.
And it's carrying CRISPR machinery to do gene-editing.
The point still stands, there are thousands of papers demonstrating preclinical utility of nanoparticles for many applications, and extremely few actual medicines.
> there are thousands of papers demonstrating preclinical utility of nanoparticles for many applications, and extremely few actual medicines.
For nanoparticle delivered mRNA, things are relatively early and relatively little is to market. But I don't think we can reasonably dismiss it as being niche or not too useful, given that we just dosed hundreds of millions of people for the biggest emergent public health issue in recent memory.
Adult cystic fibrosis patients account for like a third of all lung transplants in the US and children with CF account for like half of all pediatric lung transplants. Lung transplants cost like a million dollars, can lead to a gruesome death if rejection sets in and require lifelong drugs.
The latest, greatest drugs for CF are extremely expensive (around $250k annually last I checked), don't work for everyone and must be taken forever as well.
Standard treatments for CF are extremely expensive and the condition is extremely debilitating.
It's a good candidate for new gene editing therapies in part because there is a simple, identified issue: a defective cell channel. Some genetic disorders are more complicated than that.
As someone with CF, I remember hearing about gene therapy as a kid as far back as the late 80s. Thankfully, we didn’t have to wait for it for many CF patients to have their respiratory issues much improved or even resolved with CFTR modulators.
Last I heard, they are life changing for some people with CF. On the downside, they are typically extremely expensive (like $250k annually) and have to be taken for life and don't work for everyone. It depends on your specific CFTR defect, the CFTR being the defective cell channel at the root of all CF symptoms and pathology.
I have dropped all medical treatments except for pancreatic enzymes due to these. My pulmonary function tests came back as 104 after over a year of dropping the primary treatments for this being albuteral, "vest", and sinus surgeries. If you qualify for this medication it's life changing.
They are also brand new. For the drug as well the company is actual very helpful and realistically after insurance and the companies assistance I have paid 2, $15 co-pays the last 2 years.
With further development, these particles could offer an inhalable treatment for cystic fibrosis and other diseases of the lung
CF is not "a disease of the lungs." It's a genetic disorder that significantly impacts all epithelial tissues and mucus membranes. This includes the lungs but is not limited to the lungs.
It also includes the rest of the respiratory system, plus the gut, skin and reproductive organs. You would at a minimum need to also genetically edit the gut of CF patients to give them something vaguely resembling a normal life.
The CF community is well aware that the gut issues are significant and life threatening. The rest of the world, including medical researchers unfortunately, seems to have not gotten the memo.
Having said that, the first news of gene therapy that I read and actually liked was a guy who came up with a home therapy for his lactose intolerance.* So we potentially are at a point where you could edit both gut and lungs genetically and do some serious good for such people.
> Having said that, the first news of gene therapy that I read and actually liked was a guy who came up with a home therapy for his lactose intolerance.*
Is there any independent evidence or documentation of this? A medical study? Something corroborating? I'm not saying you're wrong, but rather extraordinary claims require extraordinary proof, and I didn't get that from watching the linked YouTube video.
It's one guy who borrowed time in a lab and treated just himself and documented it and explained the science adequately to make me stop going "Gene therapy: Clearly an evil plot."
He has a Patreon and a YouTube channel and does science videos.
I don't think any of this proves this is legitimate, however. Like I said extraordinary claims require extraordinary proof. Having a patreon and doing a follow-up shouldn't be the threshold.
That's always an acceptable means to dismiss anyone self managing their health issues better than doctors would do and making the mistake of talking about it online.
The videos make sense to me. I'm also self managing my health and get ridiculous amounts of crap off of internet strangers who also think I shouldn't be allowed to tell my story for some reason, even when other people are sharing personal health anecdotes and being well received.
This, there is a fallacy at play that individuals are unable to provide insight into health issues without an MD attached to their name and the backlash is strong.
Tbf this is partially the fault of new age medicine crap however it shouldn't be the default reaction.
Probiotics was the vertical for me that I cannot have a rational conversation with health professionals, and all they did was clean my gut up and helped my son. The how/why no one is really keen on diving into.
The videos make sense to me because they are scientifically solid but in mostly layman's terms. I have a genetic disorder and a child with the same disorder and a child who is a carrier and I know a fair amount about such things but can't always follow the medicalese, etc.
But I could readily follow the process he described of inserting the gene into a virus delivery mechanism (viruses being RNA -- ribonucleic acid -- and genes being DNA, aka 2 RNA) and how it impacted the cells lining the gut and this made the whole idea of gene therapy much more approachable for me personally and less scary.
People with CF routinely volunteer for medical experiments out of desperation and I respect their right to do that while simultaneously worrying about the real motives of the experimenters and how much to trust them. CF is a dread disease with a short life expectancy and I worry about such people being viewed like human lab rats and how that could go really bad places.
So I have enough background knowledge I don't feel his videos are a scam and I'm encouraged because many people with CF don't tolerate dairy very well. So even addressing lactose intolerance in people with CF would be life enhancing for many of them.
Can nerve agents target specific genetic traits? I don't recall that being a feature when I learned about them in the military. IIRC weapons grade nerve agents will destroy the nervous system of just about all living things and remain a risk in the environment until they have been broken down.
I use a simple agricultural nerve agent to get rid of flies. Permethrin is a sodium channel blocker that causes an overload of the CNS. Insects and very young mammals with under-developed livers can not metabolize it. So I suppose that targets a class of living things but I can not target specific breeds of flies with it. If I could then Botflies would be target numero uno.
I know you are joking, but you can't copyright ideas. If they actually write the screenplay they can protect the full text, but again, someone else may write a screenplay on the same topic if the text is not stolen from the other one.
Nitroglycerin can either alleviate heart cardiovascular disease symptoms or it can go boom. What's your point? Almost every technology is dual use if you put your mind to it.
What's the risk of lab leak? Is it impossible? Can these particles go airborne? If someone used them maliciously would anyone even figure it out? I think these are valid questions. As just one example China have been working on biological weapons [1] that can target people specific genetic characteristics and they even brag about it Col. Goo Ji Wei [2]. For all I know this could be another project to make dual-purpose weapons that can target specific groups of people. Another name for dual-purpose biological weapons is Precision Medicine [3]. Some of these weapons get funding in the name of curing diseases as part of civil-military fusion or dual-use biology.
I think most would agree that most countries would prefer not to use nukes. On the other hand there have absoutely been examples of nations committing ethnic cleansing. If China have indeed put billions into this type of research then everyone should probably also have a balance of power as well but I guess I am hoping that balance of power is created in a real legit lab with many real layers of protection and we take it more seriously than nuclear weapons.
So I suppose my point could be summed up as, Has everyone involved on this project been working in a lab that has made it near impossible for this to be abused and have all these people gone through exhaustive background and psychological testing and re-testing?
They are indeed valid questions, and the lack of actually answering the question says that they didn't know the answer but couldn't resist chiming in with a glib response.
I think you might be over estimating how effective these technologies are. Even in the most controlled circumstances, the amount of actual specific editing which occurs is probably quite low. Off target edits are likely also occuring. The focus for gene editing currently is on terminal and generally low quality of life diseases, as the low efficacy and high risk are more acceptable. We are many years out from robust and stable editing using a delivery system like this in an ideal clinic environment. Weaponizing this technology in any meaningful way is not something we probably will have to worry about in our life time. The paper is not open access so we can't know for sure what exactly they did, but it is in mice and seems to have a florescant read out, which suggests a rather crude edit (did we chop up the gene enough to turn the lights off).
We have things in the air all around us that are small, stay floating in droplets well, contagious, and self-replicating (viruses).
We know how to make things that are lethal in incredibly small doses.
Compare to this, which is not likely to stay in the air well, not self-replicating, and not-contagious, and would require larger doses for lethality.
Sure, we should be careful with any new technology, but the options to weaponize this or to have unexpected bystander externalities seems really small compared to other established technologies and risks we bear.
> What's the risk of lab leak?
I think you are latching onto the whole Sars-Cov2 concept here, but it is really a completely different situation. These lipid nanoparticles are highly unstable and require freezing, careful handling, etc. They include no amount of self replication machinery (nor any coded instructions for said machinery). There is nothing to "leak" per say. I am confident that the paper includes the specific formulations of lipids used, as well as the sequence of the payload (were it open access we could confirm).
> Can these particles go airborne?
Again, "go airborne" is a common fear with viruses. Can they mutate and gain some new function allowing them to be infectious via a new pathway. These lipid particles wont "go airborne" because they don't reproduce, they are under 0 evolutionary pressure and carry a minimal payload. It like asking if the COVID vaccine could mutate and go airborne. One could certainly spray some of these particles in the air, they will land on the nearest surface and likely break or degrade along the way. You could probably spray them on your arm and it would not result in any editing.
> If someone used them maliciously would anyone even figure it out?
If someone were able to successfully deploy a targeted genetic weapon with adverse side effects, it would likely take some time to figure out, but we absolutely have the ability and technology to figure it out today. The result would be a brand new variant in the population which has never been seen before, that looks like a CRISPR edit and is making a bunch of people of one country sick.
> Has everyone involved on this project been working in a lab that has made it near impossible for this to be abused and have all these people gone through exhaustive background and psychological testing and re-testing?
Almost certainly not. You are setting a bar pretty high for people doing pretty basic research in mice. I think we should probably setup this level of testing for all our police, military, elected officials, etc.
Citation 3 is the only one worth engaging with, and it answers most of these questions in the summary. Basically the tech is nowhere near ready (despite what some PLA general wants to pretend), and even if it was the actual targeting of a specific population is not even feasible given population genetics.
It is very okay to question the risk-benefit analysis of technologies while also understanding that they can be forces for good and evil.
For instance, Hacker News often discusses issues of privacy, asking whether new methods of finding bad actors could be misused to persecute responsible actors. It is totally fine to say "Is this good thing worthwhile if it could also cause this bad thing?"
I wonder if this could assist with rebuilding damaged lung tissue from people who have dealt with smoke inhalation from fires, industrial work, drug abuse etc.
Maybe, if there is some specific protein that you want the lungs to build that they are not already doing (or not in the quantity needed). But mostly this is going to help out for genetic diseases where it is either a protein that needs to be encourages or suppressed in the cells.
My Dad had Idiopathic Pulmonary Fibrosis (IPF) it's scarring of lung tissue. I wish there were more awareness and research for IPF. Maybe this nano protein delivering device will also help anyone with IPF too.
I had a somewhat dark hope that covid with so many people having lung issues there would be new research and medicines for IPF. But if so it's too late my Dad died in 2021. There are some drugs to treat IPF Dad was on one over $40K per year thankfully covered by insurance and the drug maker.
If live editing of cells is possible I would like to see enhancements. Say, increase VO2 capacity in our blood or something that processes lactic acid to make muscle recovery a faster process. That'd be nice.
Keep in mind that this isn't as simple as changing a YAML file to say "vo2Capacity: 2" instead of "vo2Capactiy: 1". Genes encode proteins, and those proteins perform functions based on their shapes. "Increased VO2 capacity" means making a gene that encodes a protein that has follow-on effects that accomplish that goal, which we really have no consistently good idea of how to do.
We can, for instance, add genes to plants to produce substances that bugs don't like and we can eliminate genes from animals that inhibit growth. It's not insurmountable to edit genes to "do more" or "do less"—if the answer is making more or making less of a protein we already know about. But changing the design of something is a hard challenge that we aren't good at. If increasing VO2 capacity was something that could have evolved as a beneficial mutation by way of increasing or decreasing the presence of a protein, it probably would have happened. But the fact that it hasn't either means increased VO2 capacity isn't great (eliminating muscle growth inhibition, as it turns out, isn't great) or requires more than just tweaking a protein amount.
Which is to say, gene editing is the ability to change the code. It requires separate capabilities to know what to change it to. This news is great for areas of research like cancer treatment (imagine taking a puff from an inhaler to cure your cancer, which is just ~2 gene mutations!) but much less exciting for "enhancements".
This is an old thread but here goes my answer nonetheless, I hope you get to see it.
VO2 max capacity is an adaptation that all athletes develop through cardio training, so much so that there are drugs that make this adaptation in red blood cells abnormally abundant, like Epoetin Alfa/erythropoietin. If a drug can do it, making it permanent could be possible too.
As far as we know, the drug that Lance took makes you have high blood pressure, introduces iron deficiencies and (in people with previous heart conditions) may cause cardiac insufficiency, so it's not pure benefits.
In short, your argument of 'all mutations have benefits and drawbacks' is right, but if the benefits are that high, there's no question of who'll do it but what counter-indications are you willing to put up with for the massive benefits it brings in sports (and life!) performance. Lance said he felt like a god when he was on it, he slept like 3 hours a night, rode for 12 hours a day, and won the Tour de France with it, with no sequelae, neither (according to him, so take it with a grain of salt).
Before anyone says 'just take steroids, man', I'm all in favor for a separate league of juicers in all sorts of sports, be it team sports, combat sports and solo endeavors. To me it'd be super interesting to see what humans are really capable of.
High VO2 max is heavily correlated with abilities to do things in old age, and thus survival. Considering that fragility of the elderly is a threat to their survival and quality of life, it is something worth researching.
Years ago, back when I participated on CF health lists, someone said "My child with CF turns 18 today. When he was born, life expectancy for CF was 18. It is now 36."
Since then, several CFTR modulators have become available, which are game changing for many people.
Some of our biggest breakthrough started with "in mice." Muromonab was the first monoclonal antibody approved by the FDA and came from mice. While the original had some pretty bad side effects, the entire class of biologics came from this and is capable of treating a wide variety of conditions, including essentially stopping the progression of some devastating diseases like ankylosing spondylitis and rheumatoid arthritis.
If we had reason to expect that certain people would have concerns about developments like this, then it might be best for us to address any reasonable concerns that they might have about these technologies (as much as that is possible at this stage) rather than proactively attempting to discredit them personally and marginalizing them, or else we risk providing further justification for their concerns and convincing other people that they have merit.
>>then it might be best for us to address any reasonable concerns that they might have about these technologies
That sounds lovely, but this literally does not work in the anti-vaxxer camps. They fall into two categories, the leaders who are deliberately fabricating and spreading disinformation, and the followers who are willfully remaining ignorant. They are both literally immune to facts and reason. Same for the flat-earthers, chemtrailers, 5G-causes-COVID, Bill-Gates-puts-microchips-into-vaccines, etc...and every other conspiracy theory. There are a number of papers about it I don't have the time to lookup now, but they're easy to find.
Of course, we should still disperse as widely as possible the accurate information, in detail at the outset. But we shouldn't delude ourselves to think that no conspiracy theory will arise. If it sounds technological, some arse is going to fabricate a conspiracy theory, and find followers.
> That sounds lovely, but this literally does not work in the anti-vaxxer camps. They fall into two categories, the leaders who are deliberately fabricating and spreading disinformation, and the followers who are willfully remaining ignorant. They are both literally immune to facts and reason. Same for the flat-earthers, chemtrailers, 5G-causes-COVID, Bill-Gates-puts-microchips-into-vaccines, etc...and every other conspiracy theory. There are a number of papers about it I don't have the time to lookup now, but they're easy to find.
Even worse would be to imagine that a group of people would have concerns about the use of a new technology (and to think that concerns about the use of a technology would necessarily put a person in that category of people), and to then straw-man what their supposed objections might be. I'd definitely advise against that, if our objective was to communicate in good faith and to build trust, rather than to attack, mislead, coerce and marginalize.
If there were no grounds for concern about a new technology that was currently being researched, then we might want to talk about why that is (we could write some papers on the subject for instance, I'm sure there would be some funding on offer). Or we could say "...because I said so." or cast doubt on their motivations, their capacity for critical thinking, or their scientific credentials, but arguing from authority to a skeptical audience might well be counterproductive.
We might need to admit that there may be the potential for legitimate concerns, and that we may not yet know enough about a new technology to rule them out. But the last thing we would want to do is to try to steam-roll over people's objections and drown them out (and to mislead them or misrepresent them) - that would just make people think that we're lying to them and that we have something to hide, that we're perhaps driven by a hidden motive or an over-riding ideological commitment.
> Of course, we should still disperse as widely as possible the accurate information, in detail at the outset. But we shouldn't delude ourselves to think that no conspiracy theory will arise. If it sounds technological, some arse is going to fabricate a conspiracy theory, and find followers.
There will always be conspiracy theories, nearly all of them will be harmless, and some (many, even) of them will end up being true! By their nature, governments will never stop having the temptation to misrepresent or disproportionately emphasize scientific information for political purposes, but we must do our utmost to avoid spreading official information through authoritative channels that subsequently turns out to have been knowingly inaccurate or presented in a such a way as would be likely to mislead people in serious ways, because that is a number one surefire way of destroying trust between the apparatus of the state and the population.
Transparency & perception that the government, NGOs, & corporations help rather than hurt people would help to create public trust. The problem is that there is not much reason to trust these authorities so measures to Manufacture Consent decrease in effectiveness.
Hence conspiracy theories naturally arise due to the lack of trust. Attempts to crack down on "misinformation" & "conspiracy theories" only create more distrust, & the cycle continues...until a critical mass of the population has distrust authorities. History has many examples of what happens afterwards
Another consequence of growing mistrust is that the authorities lose potency on the Geopolitical stage.
On the other hand, antibody based therapies are amazing revolutionary drugs in oncology. Chief among them is Keytruda which has improved the lives of so many patients and has $2billion in sales every month and rising. Most recently, sticking chemotherapy drugs or radioisotopes on the end of antibodies (or smaller antibody like proteins) has shown great results as a delivery vehicle. Are these ‘nanoparticles’? No, just actual drugs that work.