Dr. Kariko’s experience makes me wonder how many other potentially groundbreaking research nodes are being ignored and whether organizations like YC actually have adequate mechanisms to identify such potential bio-science startups.
"Dr. Kariko’s struggles to stay afloat in academia have a familiar ring to scientists. She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded. “When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr. David Langer ... Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention. ... “We talked to pharmaceutical companies and venture capitalists. No one cared,” Dr. Weissman said. “We were screaming a lot, but no one would listen.[1]”
i cant imagine how it must feel to have her own vaccine injected in her, and know she saved so many lives through her persistence and the rare few that believed in her through her lowest moments.
I figured there'd be a Nobel Prize for the mRNA vaccines. This is deserved and the further impacts of this are going to be felt for decades.
Some background: for many years, the flu vaccine has had what's called the "egg problem". The vaccine is cultivated in chicken eggs in a sterile environment. The US government pays billions every year to maintain these production lines. It takes about 4-5 months to go from choosing what flu strainsa are likely to be prevalent to there being a vaccine. The production line can't scale up quickly either.
Also, people who are allergic eggs can't generally take the flu vaccine. That's why they ask you.
For decades the US government has funded research to get away from this system and that resulted in the mRNA vaccine. It doesn't require chicken eggs to produce and the lead time for producing a vaccine goes to almost immediate. we saw this with Covid where the candidate vaccines were produced in days. This fed into conspiracy theories about it being unsafe because it was rushed but it was nothing more than the culmination of decades of research where fast vaccine turnaround was the entire point.
In future years we'll see mRNA vaccines turned to diseases that have thus far we've been unable to produce vaccines for.
"But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year"
The class of people who seem to do well in academia these days are those focused on grinding out masses of papers on incremental advances. Professors good at writing grant applications do well too, because with those grants they can afford to hire lots of graduate students to help with those incremental advances and masses of papers.
Individuals focused on real discovery and not publishing much until they really have something significant to say don't fit into this well.
Kariko had a PhD from Hungary, was a post-doc at Temple U. - not an elite pedigree. At Penn, an elite school:
"It was a low-level position, research assistant professor, and never meant to lead to a permanent tenured position."
and after that boss left,
"Dr. Kariko was left without a lab or financial support. She could stay at Penn only if she found another lab to take her on. “They expected I would quit,” she said.
Universities only support low-level Ph.D.s for a limited amount of time, Dr. Langer said: “If they don’t get a grant, they will let them go.” Dr. Kariko “was not a great grant writer,” ...
Kariko was slotted into the non-tenure / adjunct role, and it didn't matter what they did. It happens in private industry too. The problem is elitism overlooking talent and production. It's a brazen, obvious flaw.
The US long had the culture - imperfect, of course - of an active rejection of elitism, class, etc. 'All men are created equal', 'every man a king', meritocracy, hard work, you can accomplish anything if you work hard enough, the land of opportuity, the American Dream, etc. That equality, the respect for others, is the foundation of voting - you respect everyone's right to have input and its value.
The dominant fashion, a sort of neo-reactionaryism, is to reject that, deride it, rather than aggressively moving it forward. Many people look for ways to justify prejudice, to exclude, to embrace personal ego and greed and to mock public good. I think that's because if you embrace universal rights, opportunity, equality, etc., you can't avoid 'liberal' ideals too, and those are the target of reactionaryism.
To be honest and in this context. Nobel prize committees doesn't do any better and have history of failing in recognizing great scientific achievements until long time passes [1] (and sometimes scientists die before that which disqualify them from the prize)
I know it's a dumb cultural cite, but I keep thinking of the "12th man" scene from the movie (book too?) "World War Z". The Israeli is explaining that his job is to disagree with the consensus. Just in case. Who is then given charter and resources to plan accordingly. Just in case.
I hope there's many buckets of research funds. With a modest bucket for long shots. And perhaps a smaller bucket for loonie tunes. Where by formalizing that model would preempt all the reactionary "omgherd golden fleece!?" outbursts.
As a taxpayer, I'd be thrilled if researchers, artists, journalists, musicians, and misc crazies got some kind of UBI, to do their work without starving. Considering the scale of all the usual waste and pork, genius grants wouldn't be more than a round-off error.
With a payout of 1:1000, it'd be a bargain for society. Smartest investments ever.
Survivor bias. This is what often mentioned in any thread about business success, yet nobody has mentioned it here.
Institutions also often don't recognize researches that end up going nowhere. What we can say is that finding a gem is hard because of abundance of noise.
Is this the first practical, mass deployable remote code execution in a human? Or was there something earlier?
I particularly enjoyed the unreasonably effective antivirus bypass achieved by slight modification of the payload by introducing pseudouridine (Ψ), which the antivirus had never seen before and therefore ignored. Such a bypass definitely deserves a Nobel Prize!
I often wonder if, as a lay person, I would be capable of understanding the significance of really technical papers like this if I were to randomly start reading. Probably not without the right foundation.
I read this as an undergrad and had a blast (inside joke lol). I am considering starting a YouTube channel explaining such breakthroughs while going through the original research. If you’re interested I’ll ping you as focus group when I have some!
Well deserved. I've been following mRNA vaccines since long before the pandemic because of an interest in cancer therapeutic vaccines, and the technology is amazing and it took sooooo much fight to bring it forward to production. The speed and flexibility of the tech really is a huge advancement.
For those that know more than I do, out of curiosity, why would this Nobel go to these two and not also Özlem Türeci and Uğur Şahin? The four of them shared earlier awards, and it was Özlem Türeci and Uğur Şahin's BioNTech that got the vaccine to market (after their decades of research).
The couple are billionaires, so I'm sure they're doing just fine, but that's gotta hurt to be overlooked for such a major prize when they did so much for that discovery and technology.
Interesting -- I just got my fourth covid vaccine, along with a flu shot, yesterday. I got two shots in 2021, one in 2022, and my fourth yesterday.
Vaccines are a godsend. Also, I have never had covid.
Before you get downvoted to oblivion. I think it is a fair question.
Yes, Robert Malone could be seen as initiating the journey in 1987 [0] but there are a lot of landmark contributors who refined it to the mass-produced mRNA platform of today.
As with other Nobel Prizes, it is a far outdated award of the late 19th/early 20th century in which honoring single individuals made some sense.
In today's scientific enterprise the high-frequent collaborative effort of different teams all over the world is the norm, so over time it becomes pretty hard to single out individual scientists.
The prize winners of today are just widely recognized representatives (and therefore mostly older folks) of a particular successful scientific endeavor so that the public can still relate to the achievements via a personal story what would be otherwise a history lesson involving a lot of important people - and in this case I think Karikó's extraordinary perseverance throughout her science career fits this bill very well without ruffling up some too many feathers.
"While Malone promotes himself as an inventor of mRNA vaccines,[1][7] credit for the distinction is more often given to the lead authors on the major papers he contributed to (such as Felgner and Wolff), later advances by Katalin Karikó and Drew Weissman,[3][19] or Moderna co-founder Derrick Rossi.[13] Ultimately, mRNA vaccines were the decades-long result of the contributions of hundreds of researchers, including Malone.[3][20][21] In April 2022, Davey Alba, writing for The New York Times, said that "[w]hile he was involved in some early research into the technology, his role in its creation was minimal at best", citing "half a dozen Covid experts and researchers, including three who worked closely with Dr. Malone."[7] "[0]
The first few minutes of this video goes over what he contributed to the mRNA vaccine technology. The rest of the video debunks some claims he made on Joe Rogan.
I think we need to recognize that sometimes (often?) innovators are "kinda kooky" sometimes. In a different field, folks are surprised that a guy trying to send rockets to Mars is kinda kooky sometimes.
I wonder if she would have survived today’s even more competitive academic environment. If not then we must wonder how many future Karikos have been silenced by our current academic system.
In the times when so many people are up in arms against covid vaccines, we keep forgetting how things were and how these vaccines allowed to open up en-mass. Yes, there were problems but number of lives saved is just awe inspiring.
Some places never locked down, like Sweden and South Dakota, and their death rate wasn't significantly higher. Overall there's no evidence that lockdowns actually reduced mortality: https://onlinelibrary.wiley.com/doi/full/10.1002/hec.4737 .
>Using an event study approach and data from 43 countries and all U.S. states, we measure changes in excess deaths following the implementation of COVID-19 shelter-in-place (SIP) policies. We do not find that countries or U.S. states that implemented SIP policies earlier had lower excess deaths. We do not observe differences in excess deaths before and after the implementation of SIP policies, even when accounting for pre-SIP COVID-19 death rates.
The viral vector vaccines are a very similar development as the mRNA vaccines, and I'm curious as to why they've received less attention as a technological wonder.
Brief summary:
Goal of vaccine is to get antigens in body in order to stimulate immune response to antigen, ideally at a lower risk than via infection from associated pathogen.
- "Traditional" vaccines inject a dead or weakened pathogen. Protein subunit vaccines inject just the antigen(s). Antigen directly put in body
Both mRNA and viral vector vaccines, however, are genetic vaccines. Rather than injecting your body with the antigen directly, they inject your body with code (mRNA and DNA, respectively), with the goal of having your own body produce the antigen(s).
- mRNA vaccines deliver a snippet of mMRNA via lipid nanoparticles to your cells' cytoplasm, where your ribosomes pick it up and produce and express the antigen themselves
- viral vector vaccines deliver a snippet of code via living virus (in the case of COVID vaccines, a living adenovirus delivering a DNA payload) to your cells' nucleus, where your cells reads the DNA, produces mRNA in your cytoplasm, after which it behaves the same as the mRNA vaccines
Basically, both the mRNA vaccines and viral vector vaccines are genetic in nature and rely on delivering code to your body rather than antigens. The analogy I've used before is that traditional vaccines are SSR, and the genetic platforms are SPA. I'm just curious as to why mRNA as a platform has been so much more hyped than the viral vectors; they're novel in fundamentally the same exact way.
The 4th paragraph in the Nobel Prize press release suggests that it's because mRNA based vaccines are easier to scale up and mass produce in response to a pandemic:
"Producing whole virus-, protein- and vector-based vaccines requires large-scale cell culture. This resource-intensive process limits the possibilities for rapid vaccine production in response to outbreaks and pandemics."
Likely due to the limitations and challenges with the viral vaccines. Perhaps the biggest limitation is that the virus used as the vector must be one to which you don't already have immunity. For instance the adenovirus used by the Chinese and Russian vaccines is pretty common in the west, with something nearly half of all Americans have some immunity to it.
> "Besides injection site [muscle] and lymph nodes [proximal and distal], increased mRNA concentrations (compared to plasma levels) were found in the spleen and eye. Both tissues were examined in the frame of the toxicological studies conducted with mRNA-1273 final vaccine formulation. Low levels of mRNA could be detected in all examined tissues except the kidney. This included heart, lung, testis and also brain tissues, indicating that the
mRNA/LNP platform crossed the blood/brain barrier
A similar 2017 study was conducted using mRNA coded for luciferase as a tracking mechanism:
And it, likewise, found the protein was produced in the muscles, lymph nodes, spleen, liver, heart, bone marrow, kidney, lung, stomach, rectum, intestines, testes, and brain.
One of the main draws of using the lipid nanoparticle as a delivery mechanism for other payloads in the past has specifically been that the lipid nanoparticle can readily cross the brain-blood barrier (BBB). And the EMA paper/quotation referenced above seems to verify that this is, in fact, the case.
A question that both platforms have to contend with is: "what, if any, risks are associated with having your cells producing and expressing a pathogenic antigen that your immune system is to identify and attack?" But one that the lipid nanoparticle delivery system has to contend with is the same question, but in the context that it has very little differentiation WRT where it is going to be deployed and expressed.
With the viral vector vaccines, the delivery mechanism is a living virus, and has much more predictable infection pathways. For one, our bodies have millions of years of evolution for dealing with viral infection, and particularly safeguarding the parts of our body least desirable for infection. Viruses have a very hard time crossing the blood brain barrier, whereas lipid nanoparticles do not.
There are, meanwhile, concerns associated with the viral vector vaccines which are not associated with the mRNA vaccines, but I've yet to see this sufficiently addressed as a major shortcoming of the mRNA platform. Targeted delivery is a very important topic in the world of gene therapies, and seems to have been completely neglected in the available platforms.
Like the Oscars and Grammy's, the Nobel Prize is based as much on cultural significance as it is on the quality of the product.
Lobotomies also won the Nobel Prize because they were a cultural phenomenon of the day. JFKs sister got a lobotomy.
So even if these one and a half year old treatments prove to have significant long-term side effects there's still the recognition of the cultural and historical significance.
Very well deserved. The more we understand how RNA/DNA are able to build proteins, which then assemble into cell parts, into cells into rest of biology, the more we control our future.
I wish I’m alive to see the day when we have cheap DNA compilers and molecular assemblers. Design in CAD and a machine grows it out from a mixture of molecules in water.
Are COVID-19 vaccines the first successful mRNA-based vaccines? Seems to me there should be some other successful application of mRNA when it comes to vaccines/medications even before COVID-19. In that case, how much more complex was it to create a vaccine for COVID-19 specifically?
Nobel prize recognising effort and intent, not outcome. Didn't stop infection. Didn't stop transmission. Adverse effects overlooked and long term ones unknown.
[+] [-] Geekette|2 years ago|reply
"Dr. Kariko’s struggles to stay afloat in academia have a familiar ring to scientists. She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded. “When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr. David Langer ... Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention. ... “We talked to pharmaceutical companies and venture capitalists. No one cared,” Dr. Weissman said. “We were screaming a lot, but no one would listen.[1]”
[1] https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-k...
[+] [-] 77ko|2 years ago|reply
She had a very interesting life, I hope she writes a memoir.
Edit: She has a memoir out 10th Oct: https://www.penguinrandomhouse.com/books/706251/breaking-thr...
[+] [-] agloe_dreams|2 years ago|reply
[+] [-] swyx|2 years ago|reply
i cant imagine how it must feel to have her own vaccine injected in her, and know she saved so many lives through her persistence and the rare few that believed in her through her lowest moments.
[+] [-] pciexpgpu|2 years ago|reply
[+] [-] jmyeet|2 years ago|reply
Some background: for many years, the flu vaccine has had what's called the "egg problem". The vaccine is cultivated in chicken eggs in a sterile environment. The US government pays billions every year to maintain these production lines. It takes about 4-5 months to go from choosing what flu strainsa are likely to be prevalent to there being a vaccine. The production line can't scale up quickly either.
Also, people who are allergic eggs can't generally take the flu vaccine. That's why they ask you.
For decades the US government has funded research to get away from this system and that resulted in the mRNA vaccine. It doesn't require chicken eggs to produce and the lead time for producing a vaccine goes to almost immediate. we saw this with Covid where the candidate vaccines were produced in days. This fed into conspiracy theories about it being unsafe because it was rushed but it was nothing more than the culmination of decades of research where fast vaccine turnaround was the entire point.
In future years we'll see mRNA vaccines turned to diseases that have thus far we've been unable to produce vaccines for.
[+] [-] trauco|2 years ago|reply
About Dr. Kariko:
"But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year"
[+] [-] arbuge|2 years ago|reply
Individuals focused on real discovery and not publishing much until they really have something significant to say don't fit into this well.
[+] [-] wolverine876|2 years ago|reply
Kariko had a PhD from Hungary, was a post-doc at Temple U. - not an elite pedigree. At Penn, an elite school:
"It was a low-level position, research assistant professor, and never meant to lead to a permanent tenured position."
and after that boss left,
"Dr. Kariko was left without a lab or financial support. She could stay at Penn only if she found another lab to take her on. “They expected I would quit,” she said.
Universities only support low-level Ph.D.s for a limited amount of time, Dr. Langer said: “If they don’t get a grant, they will let them go.” Dr. Kariko “was not a great grant writer,” ...
Kariko was slotted into the non-tenure / adjunct role, and it didn't matter what they did. It happens in private industry too. The problem is elitism overlooking talent and production. It's a brazen, obvious flaw.
The US long had the culture - imperfect, of course - of an active rejection of elitism, class, etc. 'All men are created equal', 'every man a king', meritocracy, hard work, you can accomplish anything if you work hard enough, the land of opportuity, the American Dream, etc. That equality, the respect for others, is the foundation of voting - you respect everyone's right to have input and its value.
The dominant fashion, a sort of neo-reactionaryism, is to reject that, deride it, rather than aggressively moving it forward. Many people look for ways to justify prejudice, to exclude, to embrace personal ego and greed and to mock public good. I think that's because if you embrace universal rights, opportunity, equality, etc., you can't avoid 'liberal' ideals too, and those are the target of reactionaryism.
[+] [-] elashri|2 years ago|reply
[1] https://www.nature.com/articles/d41586-023-03086-3
[+] [-] specialist|2 years ago|reply
I know it's a dumb cultural cite, but I keep thinking of the "12th man" scene from the movie (book too?) "World War Z". The Israeli is explaining that his job is to disagree with the consensus. Just in case. Who is then given charter and resources to plan accordingly. Just in case.
I hope there's many buckets of research funds. With a modest bucket for long shots. And perhaps a smaller bucket for loonie tunes. Where by formalizing that model would preempt all the reactionary "omgherd golden fleece!?" outbursts.
As a taxpayer, I'd be thrilled if researchers, artists, journalists, musicians, and misc crazies got some kind of UBI, to do their work without starving. Considering the scale of all the usual waste and pork, genius grants wouldn't be more than a round-off error.
With a payout of 1:1000, it'd be a bargain for society. Smartest investments ever.
[+] [-] relativ575|2 years ago|reply
Institutions also often don't recognize researches that end up going nowhere. What we can say is that finding a gem is hard because of abundance of noise.
[+] [-] kevmo|2 years ago|reply
[+] [-] f6v|2 years ago|reply
Unlike industry, where there’s no internal politics and everything is merit-based.
[+] [-] IOT_Apprentice|2 years ago|reply
[+] [-] unknown|2 years ago|reply
[deleted]
[+] [-] H8crilA|2 years ago|reply
I particularly enjoyed the unreasonably effective antivirus bypass achieved by slight modification of the payload by introducing pseudouridine (Ψ), which the antivirus had never seen before and therefore ignored. Such a bypass definitely deserves a Nobel Prize!
[+] [-] aredox|2 years ago|reply
mRNA tech is just cutting out a lot of cruft and mass-producing and delivering tiny mRNA strands directly.
[+] [-] xorcist|2 years ago|reply
Not the other way around...
[+] [-] Beijinger|2 years ago|reply
The real question is now: When will it be used in doping? Honestly, I suspect it might be already.
[+] [-] happytiger|2 years ago|reply
[+] [-] unknown|2 years ago|reply
[deleted]
[+] [-] anonu|2 years ago|reply
I often wonder if, as a lay person, I would be capable of understanding the significance of really technical papers like this if I were to randomly start reading. Probably not without the right foundation.
[+] [-] ramraj07|2 years ago|reply
I read this as an undergrad and had a blast (inside joke lol). I am considering starting a YouTube channel explaining such breakthroughs while going through the original research. If you’re interested I’ll ping you as focus group when I have some!
[+] [-] j7ake|2 years ago|reply
This is an example where even citations fail to recognise significant papers.
The Doudna Charpentier paper, by contrast, has been cited 17k times and publishes only 12 years ago.
As a fun exercise, the journal immunity should provide the reviewer comments to see how things have changed in light of 20 years.
[+] [-] ortusdux|2 years ago|reply
[+] [-] anuvrat1|2 years ago|reply
[+] [-] epistasis|2 years ago|reply
[+] [-] brutusborn|2 years ago|reply
[+] [-] mtalantikite|2 years ago|reply
The couple are billionaires, so I'm sure they're doing just fine, but that's gotta hurt to be overlooked for such a major prize when they did so much for that discovery and technology.
[+] [-] jononomo|2 years ago|reply
[+] [-] xdennis|2 years ago|reply
[+] [-] dav_Oz|2 years ago|reply
Yes, Robert Malone could be seen as initiating the journey in 1987 [0] but there are a lot of landmark contributors who refined it to the mass-produced mRNA platform of today.
As with other Nobel Prizes, it is a far outdated award of the late 19th/early 20th century in which honoring single individuals made some sense.
In today's scientific enterprise the high-frequent collaborative effort of different teams all over the world is the norm, so over time it becomes pretty hard to single out individual scientists.
The prize winners of today are just widely recognized representatives (and therefore mostly older folks) of a particular successful scientific endeavor so that the public can still relate to the achievements via a personal story what would be otherwise a history lesson involving a lot of important people - and in this case I think Karikó's extraordinary perseverance throughout her science career fits this bill very well without ruffling up some too many feathers.
[0]https://archive.ph/xgmnv
[+] [-] Geekette|2 years ago|reply
[0] https://en.wikipedia.org/wiki/Robert_W._Malone
[+] [-] kreskin|2 years ago|reply
https://www.youtube.com/watch?v=xjszVOfG_wo
[+] [-] jimmydddd|2 years ago|reply
[+] [-] j7ake|2 years ago|reply
I wonder if she would have survived today’s even more competitive academic environment. If not then we must wonder how many future Karikos have been silenced by our current academic system.
[+] [-] sytelus|2 years ago|reply
[+] [-] logicchains|2 years ago|reply
>Using an event study approach and data from 43 countries and all U.S. states, we measure changes in excess deaths following the implementation of COVID-19 shelter-in-place (SIP) policies. We do not find that countries or U.S. states that implemented SIP policies earlier had lower excess deaths. We do not observe differences in excess deaths before and after the implementation of SIP policies, even when accounting for pre-SIP COVID-19 death rates.
[+] [-] shrubble|2 years ago|reply
[+] [-] ralusek|2 years ago|reply
Brief summary:
Goal of vaccine is to get antigens in body in order to stimulate immune response to antigen, ideally at a lower risk than via infection from associated pathogen.
- "Traditional" vaccines inject a dead or weakened pathogen. Protein subunit vaccines inject just the antigen(s). Antigen directly put in body
Both mRNA and viral vector vaccines, however, are genetic vaccines. Rather than injecting your body with the antigen directly, they inject your body with code (mRNA and DNA, respectively), with the goal of having your own body produce the antigen(s).
- mRNA vaccines deliver a snippet of mMRNA via lipid nanoparticles to your cells' cytoplasm, where your ribosomes pick it up and produce and express the antigen themselves
- viral vector vaccines deliver a snippet of code via living virus (in the case of COVID vaccines, a living adenovirus delivering a DNA payload) to your cells' nucleus, where your cells reads the DNA, produces mRNA in your cytoplasm, after which it behaves the same as the mRNA vaccines
Basically, both the mRNA vaccines and viral vector vaccines are genetic in nature and rely on delivering code to your body rather than antigens. The analogy I've used before is that traditional vaccines are SSR, and the genetic platforms are SPA. I'm just curious as to why mRNA as a platform has been so much more hyped than the viral vectors; they're novel in fundamentally the same exact way.
[+] [-] nyc|2 years ago|reply
"Producing whole virus-, protein- and vector-based vaccines requires large-scale cell culture. This resource-intensive process limits the possibilities for rapid vaccine production in response to outbreaks and pandemics."
[+] [-] inferiorhuman|2 years ago|reply
[+] [-] ralusek|2 years ago|reply
In particular, the delivery of the mRNA payload is done via lipid nanoparticles that are not in any way targeted to a specific cell type.
The European Medicines Agency released a report on the distribution of the mRNA found in various organs:
https://www.ema.europa.eu/en/documents/assessment-report/spi...
> "Besides injection site [muscle] and lymph nodes [proximal and distal], increased mRNA concentrations (compared to plasma levels) were found in the spleen and eye. Both tissues were examined in the frame of the toxicological studies conducted with mRNA-1273 final vaccine formulation. Low levels of mRNA could be detected in all examined tissues except the kidney. This included heart, lung, testis and also brain tissues, indicating that the mRNA/LNP platform crossed the blood/brain barrier
A similar 2017 study was conducted using mRNA coded for luciferase as a tracking mechanism:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5475249/
And it, likewise, found the protein was produced in the muscles, lymph nodes, spleen, liver, heart, bone marrow, kidney, lung, stomach, rectum, intestines, testes, and brain.
One of the main draws of using the lipid nanoparticle as a delivery mechanism for other payloads in the past has specifically been that the lipid nanoparticle can readily cross the brain-blood barrier (BBB). And the EMA paper/quotation referenced above seems to verify that this is, in fact, the case.
A question that both platforms have to contend with is: "what, if any, risks are associated with having your cells producing and expressing a pathogenic antigen that your immune system is to identify and attack?" But one that the lipid nanoparticle delivery system has to contend with is the same question, but in the context that it has very little differentiation WRT where it is going to be deployed and expressed.
With the viral vector vaccines, the delivery mechanism is a living virus, and has much more predictable infection pathways. For one, our bodies have millions of years of evolution for dealing with viral infection, and particularly safeguarding the parts of our body least desirable for infection. Viruses have a very hard time crossing the blood brain barrier, whereas lipid nanoparticles do not.
There are, meanwhile, concerns associated with the viral vector vaccines which are not associated with the mRNA vaccines, but I've yet to see this sufficiently addressed as a major shortcoming of the mRNA platform. Targeted delivery is a very important topic in the world of gene therapies, and seems to have been completely neglected in the available platforms.
[+] [-] strangesmells02|2 years ago|reply
Lobotomies also won the Nobel Prize because they were a cultural phenomenon of the day. JFKs sister got a lobotomy.
So even if these one and a half year old treatments prove to have significant long-term side effects there's still the recognition of the cultural and historical significance.
[+] [-] nojvek|2 years ago|reply
I wish I’m alive to see the day when we have cheap DNA compilers and molecular assemblers. Design in CAD and a machine grows it out from a mixture of molecules in water.
[+] [-] reqo|2 years ago|reply
[+] [-] sergiogjr|2 years ago|reply
[+] [-] EchoReflection|2 years ago|reply
[+] [-] unknown|2 years ago|reply
[deleted]