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Drugs of the future will be easier and faster to make, thanks to mRNA

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By Li Li

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the COVID-19 mRNA vaccines brought a new approach to vaccine development 

They certainly did.

With the increase of life-threatening conditions of over 4,400% after the rollout of the mRNA rollout over the previous two and half years - not seen during the 2009 H1N1 vaccination campaign - the most diplomatic statement I believe anyone could make at this point would be, there must be an increase in additional, unbiased research to better understand the vaccines long-term effects, and why the short term risks are evidence that a positive long-term outlook seems extremely unlikely.

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Until the issues of ( 1. ) biodistribution and ( 2. ) frameshiftings errors (a consequence of the inclusion of pseudouridine) are properly addressed, I'll be sticking with traditional vaccines.

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Hysterical

Interesting. Yes, what would definitely not be hysterical would the continued, unwavering support of the former CMA, who admitted that masking and the "6 feet apart” social distancing recommendation was not based on science, but just "kind of appeared", and, more sinisterly, is shrouded by the revelations that he funded - through through Eco Health Alliance - the Wuhan Institute of Virology lab that performed gain of function experiments - a practice that has been made illegal in the US.

That would definitely not be hysterical would it Roy?

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What does any of that have to do with the 4,400% increase?

It clearly demonstrates and speaks volumes about which sources you angrily chide as being from "cranks" and which particular narrative you illogically elect to believe.

Always good fun when the truth comes to light.

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It would be regrettable to read this column and not to also consider some important research described and published last month in the Proceedings of the National Academy of Sciences.

Entitled Combinatorial design of ionizable lipid nanoparticles for muscle-selective mRNA delivery with minimized off-target effects. (Link below).

But don’t let the title scare you away, without first reading some of the promise being held inside. And yes, first, we will - as we should - recognize that there is a patent application pending by the authors over this technology. And also that much more work needs to be done.

But the oncology study indicates that a new lipid nanoparticle has shown “exceptional” mRNA delivery efficiency in muscle tissues while minimizing unintended mRNA translation other tissues and organs, while causing “potent cellular immune responses, even with limited expression observed in lymph nodes.”

As the authors explain in their press release last month (link below),

many LNP designs can inadvertently result in substantial mRNA expression in off-target tissues and organs like the liver or heart, resulting in often treatable but unwanted side effects. The drive to improve the safety of mRNA therapies that have the potential to treat a broad range of diseases means there is an urgent need for LNPs designed to minimize these off-target effects.

They continue by contrasting their finding that, compared to the LNP developed by the Massachusetts-based biotechnology company Moderna, their iso-A11B5C1, that it:

demonstrated a high level of muscle-specific mRNA delivery efficiency. It also triggered a different kind of immune response than what is seen in vaccines used to treat infectious diseases. Interestingly, iso-A11B5C1 triggered a lower humoral immune response, typically central to current antibody-focused vaccines, but still elicited a comparable cellular immune response.

Again, this is early work. But it does show some welcome progress towards delivery with precision, while reducing risks seen in mRNA delivery under certain specific circumstances. No, there are no signs as of yet that risks can be eliminated using mRNA technology, but there is progress towards minimizing or limiting it.

http://dx.doi.org/10.1073/pnas.2309472120

https://www.pharmacy.utoronto.ca/news-announcements/scientists-discover-new-lipid-nanoparticle-shows-muscle-specific-mrna-delivery-reduces-target-effects

4 ( +6 / -2 )

With the increase of life-threatening conditions of over 4,400% after the rollout of the mRNA rollout

No such thing happened. When you need to use debunked information to support what you believe you are making clear you are not actually interested on what is best for public health, just push your personal beliefs.

Until the issues of ( 1. ) biodistribution and ( 2. ) frameshiftings errors (a consequence of the inclusion of pseudouridine) are properly addressed, I'll be sticking with traditional vaccines.

None of these issues have any demonstrated clinical importance, the diseases against which the technology is being used on the other hand represents a much higher risk for the health.

the Wuhan Institute of Virology lab that performed gain of function experiments - a practice that has been made illegal in the US.

that is also completely false, if gain of function was illegal not even basic work could be done for pathogens, especially viruses.

It clearly demonstrates and speaks volumes about which sources you angrily chide as being from "cranks" and which particular narrative you illogically elect to believe.

You present no source for the debunked claim, that means even a terribly bad source still triumphs over yours, when that "source" is actually the whole scientific community of the world in general it becomes clear who is in the right, and that would not be the baseless claims.

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Again, this is early work. But it does show some welcome progress towards delivery with precision, while reducing risks seen in mRNA delivery under certain specific circumstances. No, there are no signs as of yet that risks can be eliminated using mRNA technology, but there is progress towards minimizing or limiting it.

It is a very interesting time for drug delivery right now, but I feel more optimistic with the recent developments with exosome containing viral vectors, combining the relatively high efficiency of exosomes with the specificity of a viral vector may be a huge step forward. The best thing is that creating these "vexosomes" is a relatively simple process once you have both components ready, so it should not increase costs importantly.

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Until the issues of ( 1. ) biodistribution and ( 2. ) frameshiftings errors (a consequence of the inclusion of pseudouridine) are properly addressed, I'll be sticking with traditional vaccines.

Agreed with these undisputed matters.

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Agreed with these undisputed matters

As prove by the references already provided, included in the undisputed part of the matter is that they do not have any real clinical importance.

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Until the issues of ( 1. ) biodistribution and ( 2. ) frameshiftings errors (a consequence of the inclusion of pseudouridine) are properly addressed, I'll be sticking with traditional vaccines.

True, as these important factors still need to be investigated, according to the experts.

former CMA, who admitted that masking and the "6 feet apart” social distancing recommendation was not based on science, 

Then again, it has been proven we can't trust all the experts. In addition, some place blind faith in the hands of fake experts who provide conflicting "advice"--wear masks, don't wear masks. Like the WHO agency.

https://edition.cnn.com/2020/03/30/world/coronavirus-who-masks-recommendation-trnd/index.html

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Exosomes are an interesting and promising area in oncology. We have some serious indications over how exosomes in a TME are an important / critical factor in those cancer cells that are capable of self-renewing themselves and servicing tumor growth and recurrence. Break this cycle and you break command and control over influence of neighboring or susceptable cells. Exosomes being the suspect over how they multivesicular endosomes join with a cell's outer membrane, to release their ugly little payloads. Lots more work needs to be shown before this line of inquiry makes it into the field, though.

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True, as these important factors still need to be investigated, according to the experts.

The experts clearly and unequivocally have determined the issue have no real clinical importance, nor that it would make the interventions less desirable than not doing anything.

Then again, it has been proven we can't trust all the experts. 

Especially when someone claim something against the scientific consensus and use nameless "experts" without any reference to supposedly support that claim.

https://edition.cnn.com/2020/03/30/

Even worse when someone tries to use a reference almost 4 years old to supposedly prove what the experts are saying now, which is not at all conflicting.

https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-covid-19-masks

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Lots more work needs to be shown before this line of inquiry makes it into the field, though

Yes, acting against pathological effects from exosomes is very complicated thing, but fortunately using the exosomes as a delivery system appears to be much more straightforward. As long as proper care is taken about the cells used as source there is a lot of freedom about what can be packaged in them, LNP may be good enough for naked mRNA of one single variety, but using exosomes opens the door to many other combinations.

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the mRNA in the Pfizer-BioNTech and Moderna COVID-19 vaccines directs cells to produce a harmless version of the virus’ spike protein

It is not harmless. The serious adverse events are off the charts, and the large increase in excess deaths after the roll out of these shots.

that trains the immune system to recognize and better prepare for potential infection.

Yeah, trains the immune system to attack any virus in the blood stream (not in the nasopharynx and lungs) with the same spike protein. Unfortunately, the spike protein changes too much. Natural infection trains the immune system to recognize multiple viral proteins, with IgA antibodies directed to the nasopharynx and lungs.

And after a few doses your body produces unwanted IgG4 antibodies.

So I very much agree with Jay's comment:

there must be an increase in additional, unbiased research to better understand the vaccines long-term effects, and why the short term risks are evidence that a positive long-term outlook seems extremely unlikely.

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Even worse when someone tries to use a reference almost 4 years old to supposedly prove what the experts are saying now, which is not at all conflicting.

It is a great source to show the flip flopping of these so called "experts".

It is not harmless. The serious adverse events are off the charts, and the large increase in excess deaths after the roll out of these shots.

Absolutely; this is well-documented.

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Further advancements have the potential to enable a new generation of safe, durable and effective mRNA

You mean the potential to "finally" produce them?

Two years ago, the CDC denied the vaccines caused heart damage. So, that's changed:

https://news.yahoo.com/side-effects-covid-booster-185533078.html

Why?

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It is not harmless. The serious adverse events are off the charts

No they are not this claim has been repeatedly debunked by the experts and that is why not even one actual institution of medical science say this is true.

and the large increase in excess deaths after the roll out of these shots.

Increases depending on covid? that is the whole point to reduce them thanks to the vaccines.

Natural infection trains the immune system to recognize multiple viral proteins, with IgA antibodies directed to the nasopharynx and lungs.. 

And that has done absolutely anything to prevent repeated reinfections, which is precisely why vaccines are still being recommended.

And after a few doses your body produces unwanted IgG4 antibodies

Not to the point of having any clinical importance, the alternative (getting infected) on the other hand has been already correlated as the cause of multiple elevations of risk to the health of the patients.

Not really a hard choice, immunizations are still the much safer option.

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It is a great source to show the flip flopping of these so called "experts".

What you call "flip flopping" is actually science based medical recommendations. What would be irrational is to expect recommendations to be based on things that will be known in the future.

Absolutely; this is well-documented.

Actually it is the opposite, there is not any actually peer reviewed report that says this, only obvious manipulations and imaginary data that people tried to use to say this, and that was immediately debunked by actual experts.

This is why people making this claim do not even try to use that reference, it has been so completely destroyed that any attempt to use it gets immediately called even by people without knowledge about the topic.

You mean the potential to "finally" produce them?

The current vaccines are already proved to be safe and effective, to the consternation of the antivaxxer groups that tried to mislead the public and said the opposite, they were all demonstrated wrong.

Two years ago, the CDC denied the vaccines caused heart damage. So, that's changed:

The situation is the same, the CDC and every other important institution still says vaccines REDUCE the risk from hearth damage simply because the infection is much more closely correlated with the problem.

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Hey there Roy. Thanks for the links to the blog posts. I always enjoy food for thought!

( 1. ) With regards to the frameshift error, the paper that first identified the problem was published December 6th, 2023. I would argue that there simply hasn’t been time to extensively research whether incorrect proteins resulting from frameshift errors are linked to adverse outcomes in those who got the mRNA vaccines or not.

In the blog you linked to the author dismisses such a possibility saying, “we do know what such adverse outcomes would probably look like. It would likely look the same as any other errant immune reaction or autoimmune condition.”

Oddly enough there just happen to have been reports of new-onset autoimmune diseases after vaccination. In the interest of patient safety, this at least warrants further investigation, no?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108562/

( 2. ) In the very blog post you post in response to my concern about a lack of cell targeting it acknowledges that Pfizer’s own LNP pharmacokinetic study for PMDA showed, albeit in a rodent model, that only 53% of LNP stayed within the intramuscular injection site. 

More recent studies, performed on newly deceased patients, provide more evidence of widespread biodistribution, including uptake by cells in the myocardium. 

https://www.nature.com/articles/s41541-023-00742-7

Personally, given that the average age of death 'either due' to or 'involving' COVID-19 is roughly 80yo, the risk from LNP + mRNA platform are currently one I’m not willing to take. But don’t let my misgivings influence you. By all means, please go get your bi-annual boosters!  I hope you're right and I'm wrong.

https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/singleyearofageandaverageageofdeathofpeoplewhosedeathwasduetoorinvolvedcovid19

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Oddly enough there just happen to have been reports of new-onset autoimmune diseases after vaccination

There is a huge difference between theorizing how disease might be produced by something and showing evidence of that actually happening. Since a huge number of people have been vaccinated there would be reports of everything happening after vaccination, the important part would be to demonstrate a higher incidence of such problems in vaccinated people compared with unvaccinated ones, which is not the case.

Personally, given that the average age of death 'either due' to or 'involving' COVID-19 is roughly 80yo

This data only includes acute deaths, and the shift towards eariler deaths is already evident, since it is already known that covid increases the risk for many other health problems even after the acute infection, that means pretending the this risk is not worth to be taken into account is not a valid position to take. Specially when you are trying to compare this with vaccines that have not been correlated with increased risks of death compared with unvaccinated people.

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No, it is in fact the opposite, as you have been shown many times.

Not even once, by anybody. As easily proved as you are unable to bring any reference where this is "shown" No clinical importance at all.

And your source is . . .none.

The source is the already provided one, the same, it is what is included. What source do you imagine is necessary to prove THIS already provided source have this limitation?

The actual science conflicted with the WHO's erroneous opinion over and over.

No, not at all. That is only what you personally claimed, the CDC as well as other medical science institutions had the same recommendations that also changed after evidence was collected.

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I openly recognise he has arguments that successfully defend his position

He used zero arguments to defend his original position from the valid criticisms that refuted it, what arguments are you recognizing if there are none.

And often your references you sparsely post don't even support the issue you are trying to promote; false references.

The arguments are the ones disproving the personal claim made from the offered reference, once again the reference is the same, the argument is that it does not include relevant information. Something that has not been refuted by any contrary argument, even if you think you can recognize these inexistent arguments.

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