A short history of messenger RNA

[minnie616]

Research on producing a Messenger RNA began in the 1990s

A short history of messenger RNA
DNA stores the instructions cells use to make proteins. Messenger RNA (mRNA) is just as important: It carries the genetic code from the DNA to the protein-making machinery. Despite being relatively easy to produce, no mRNA vaccine had ever won approval prior to the COVID pandemic. When research began in the 1990s, it was considered too outlandish to gain any support or funding. In fact, Katalin Kariko, the researcher who finally cracked the code, was demoted at the University of Pennsylvania for her lack of progress.

Despite her theory making biological sense, the immune system would quickly destroy any synthetic RNA it found. Ten years after her demotion, Kariko solved the mystery and published a series of papers. That research caught the eye of at least two scientists, the ones who would go on to found Moderna and BioNTech.

Fast-forward to 2021, and those companies have multiple drug candidates in their respective pipelines to fight viral illnesses, cancer, and other diseases. Moderna has 27 candidates at some stage of clinical development while BioNTech has 22.

Of course, both also now have authorized vaccines for COVID-19.

https://www.fool.com/investing/2021/04/06/pfizers-ceo-makes-a-claim-that-might-shock-anyone/

 

[lemmiwinx]

I got both Pfizer shots a few months ago. So far I'm not growing any extra appendages out of my forehead but you never know.

 

[Pippi Longstock]

Research on producing a Messenger RNA began in the 1990s




https://www.fool.com/investing/2021/04/06/pfizers-ceo-makes-a-claim-that-might-shock-anyone/

Might be a dumb question but why does the vaccine mRNA cause more side effects after the second jab?

 

[KevinKohler]

I'm more concerned about Johnson and Johnson finding a way to slip some asbestos into their shots.

 

[noonereal]

Research on producing a Messenger RNA began in the 1990s




https://www.fool.com/investing/2021/04/06/pfizers-ceo-makes-a-claim-that-might-shock-anyone/

so what is your point?

Thanks

 

[Demon]

so what is your point?

Thanks

Background information?

 

[Mongidig]

I got both Pfizer shots a few months ago. So far I'm not growing any extra appendages out of my forehead but you never know.

Lets give it a couple more weeks and see what happens.

 

[minnie616]

Might be a dumb question but why does the vaccine mRNA cause more side effects after the second jab?

Not , a dumb question.

The second shot may trigger the immune to react more to the snippet of genetic code the second time it is deleted.


The mRNA vaccines consist of a snippet of genetic code directing production of the coronavirus' spike protein. That snippet is delivered in a tiny fat bubble called a lipid nanoparticle.

A persons immune system may respond to that delivery and that causes the short-term side effects.

 

[joko104]

Research on producing a Messenger RNA began in the 1990s




https://www.fool.com/investing/2021/04/06/pfizers-ceo-makes-a-claim-that-might-shock-anyone/

I will not nitpick your thread and I'm open to learning more. I am a rare person who (rarely) can change my mind.

Not reading it all yet, this was not reassuring:

"Pfizer might have built out an impressive network of mRNA manufacturing and logistics in 2020, but scientifically its last year was a bust. Ibrance, its key breast cancer drug, failed its attempt to become an early-stage treatment. Its arthritis medicine, Xeljanz, showed an increased risk of heart attack and cancer compared to alternative treatments."

To prior mRNA tests on humans both proved a bust - and one increasing the risk of cancer and heart attack by comparison. And that is 2020 or 2019 - hard to tell. There hasn't been enough time to learn if the Pfizer covid-19 test increases the risk of heart attack, cancer or other severe and lethal side effects.

Unless I misinterpreted that paragraph or it is a misstatement, that is concerning. I do read all drug warning labels - OTC or prescription. I take warnings carefully and seriously. I do not think "they just have to say that to avoid lawsuits." Almost everyone has used it for years and thousands of doctors prescribe it including my own is not persuasive enough. If prescription I research it online. I also read the Ingredients list and the breakdown it terms of calories, cholesterol, sugar, salt, any transfat etc.

Anyway, thank you for this thread. I would really like to learn more about this in detail in terms of development, the companies, how they say it works, and can they prove the claim? My greatest concern is long term health effects. I know I'm not going to be harmed at the time of the vaccine, although a little concerned. I think more about 5 or 10 years from now.

 

[minnie616]

I will not nitpick your thread and I'm open to learning more. I am a rare person who (rarely) can change my mind.

Not reading it all yet, this was not reassuring:

"Pfizer might have built out an impressive network of mRNA manufacturing and logistics in 2020, but scientifically its last year was a bust. Ibrance, its key breast cancer drug, failed its attempt to become an early-stage treatment. Its arthritis medicine, Xeljanz, showed an increased risk of heart attack and cancer compared to alternative treatments."
...

Anyway, thank you for this thread. I would really like to learn more about this in detail in terms of development, the companies, how they say it works, and can they prove the claim? My greatest concern is long term health effects. I know I'm not going to be harmed at the time of the vaccine, although a little concerned. I think more about 5 or 10 years from now.

...

Here is an article with more detail if you are interested.

https://www.nature.com/scitable/topicpage/chemical-structure-of-rna-348/


mRNA and Splicing


Figure 4

Several forms of RNA play pivotal roles in gene expression—the process responsible for manifesting the instructions stored in the sequence of DNA nucleotides in either RNA or protein molecules that carry out the cell's activities (Figures 4 & 5). Messenger RNA (mRNA) is particularly important in this process. mRNA is primarily composed of coding sequences; that is, it carries the genetic information for the amino acid sequence of a protein to the ribosome, where that particular protein is synthesized. In addition, each mRNA molecule also contains noncoding, or untranslated, sequences that may carry instructions for how the mRNA is handled by the cell (Figure 6). For example, the untranslated region at the 5' end of the mRNA molecules found in bacteria and other prokaryotes contains what is called a Shine-Dalgarno sequence, which aids in the binding of the mRNA In contrast, the mRNA of eukaryotic organisms is prepared for translation through ...

 

[Ethel2]

Not , a dumb question.

The second shot may trigger the immune to react more to the snippet of genetic code the second time it is deleted.


The mRNA vaccines consist of a snippet of genetic code directing production of the coronavirus' spike protein. That snippet is delivered in a tiny fat bubble called a lipid nanoparticle.

A persons immune system may respond to that delivery and that causes the short-term side effects.

Its the immune systems response to the spike protein, not to the mRNA, that causes the reaction. The first shot primes the system; the second time around the immune system is ready and already primed. The response is much stronger the second time. There is a medical term for it but I can’t remember what it is atm.

 

[Noodlegawd]

Might be a dumb question but why does the vaccine mRNA cause more side effects after the second jab?

The side effects are caused by your immune system reacting to the presence of the foreign antigen (which is synthesized by your own cells based on the mRNA template that is contained in the vaccine) in your body.

When you get the first shot, your immune system doesn't recognize the antigen as quickly. So the reaction to it is not as quick or as strong.

When you get the second shot, your immune system has already been primed to recognize the specific antigen, and therefore reacts more suddenly and strongly to it.

 

[calamity]

Research on producing a Messenger RNA began in the 1990s




https://www.fool.com/investing/2021/04/06/pfizers-ceo-makes-a-claim-that-might-shock-anyone/

Well, looks like we can thank the 90's for our 2021 vaccines. I guess that means Clinton did it.

j/k

 

[Ethel2]

Here’s a decent summary of why the secondary response is much faster and stronger:

Primary vs. Secondary Immune Response • Microbe Online

Primary immune response to Ag occurs on the first occasion. Subsequent encounter of B and T cells with same Ag leads to secondary response.

microbeonline.com

 

[lemmiwinx]

Lets give it a couple more weeks and see what happens.

As I speak now I'm having trouble finding my car keys. This usually happens after my third cocktail and I've suddenly noticed I'm totally out of rum.

 

[minnie616]

I will not nitpick your thread and I'm open to learning more. I am a rare person who (rarely) can change my mind.

Not reading it all yet, this was not reassuring:

"Pfizer might have built out an impressive network of mRNA manufacturing and logistics in 2020, but scientifically its last year was a bust. Ibrance, its key breast cancer drug, failed its attempt to become an early-stage treatment. Its arthritis medicine, Xeljanz, showed an increased risk of heart attack and cancer compared to alternative treatments."
....

Actually , Ibrance and Xelijanz are not mRNA drugs. Pfizer partered with BioNTec for a Covid they were not trying to manufacture a mRNA vaccine.

Ibrance was first approved by the U.S. Food and Drug Administration in 2015. The drug is indicated for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or men.

On May 30, 2018, the US Food and Drug Administration (FDA) expanded the indication of tofacitinib (Xeljanz; Pfizer), an oral Janus kinase (JAK) inhibitor, for the treatment of adults with moderately to severely active ulcerative colitis.

 

[RAMOSS]

Might be a dumb question but why does the vaccine mRNA cause more side effects after the second jab?

Because the side effects are caused by your immune system kicking in, .. that would be true of any 'two shot' vaccine, not just mrna.

 

[Pippi Longstock]

What I'm getting is that the mRNA vaccine produce the needed thing. as opposed to automatically taking care of it. I hope that makes sense. That is the word I focused on in the microbio online information.

 

[minnie616]

Well, looks like we can thank the 90's for our 2021 vaccines. I guess that means Clinton did it.

j/k

Yes, in fact the first mRNA vaccine prototype was delveloped around 2009 or 2010 to combat the SARS coronavirus.


The United States already had a prototype vaccine that was the SARS coronavirus which shares 80 percent of the makeup of Covid 19.

The SARS-CoV1 Coronavirus of 2003 and the CoV 19 Coronavirus ( SARS-CoV2 ) virus share 80 percent of the same make up.

Several years after the SARS Coronavirus had been contained and had died out a mRNA vaccine for SARS-CoV had been developed in Texas.

It was ready to be tested on humans but it never reached that stage because it lacked the funding.

It was hard to get the funding because SARS was no longer a threat.

But since SARS had jumped from animal to humans there was always the chance it might come back in the original form or a similar form.

The protovaccine was stored in the National Stockpile in case we needed it in the future.

The vaccine manufacturers just had to adjust the vaccine form to attack the Covid 19 virus instead of attacking the SARS virus.

 

[Ethel2]

What I'm getting is that the mRNA vaccine produce the needed thing. as opposed to automatically taking care of it. I hope that makes sense. That is the word I focused on in the microbio online information.

mRNA enters a ribosome where the spike protein is assembled.

 

[Pippi Longstock]

I have been noticing a trend that some people are deciding not to get the second dose of mRNA vaccine. They say that the first dose provides enough protection. How does that factor in? is it dangerous to the body to not finish the process of assembling the whole thing?

 

[Ethel2]

I have been noticing a trend that some people are deciding not to get the second dose of mRNA vaccine. They say that the first dose provides enough protection. How does that factor in? is it dangerous to the body to not finish the process of assembling the whole thing?

It’s only dangerous in that while the first dose does protect you (about 80% of the time) its not the kind of long lasting protection (ie, likely much longer than with just a single dose) that a second dose provides. Most immunizations work that way-you need a booster shot.

Btw, breakthrough infections have been occurring but the concerning part to me is that some breakthrough infections have led (rarely) to hospitalizations and deaths. I’ll try to find the numbers reported from states that keep track of this. I read it in a medical blog I subscribe to.

 

[Ethel2]

It’s only dangerous in that while the first dose does protect you (about 80% of the time) its not the kind of long lasting protection (ie, likely much longer than with just a single dose) that a second dose provides. Most immunizations work that way-you need a booster shot.

Btw, breakthrough infections have been occurring but the concerning part to me is that some breakthrough infections have led (rarely) to hospitalizations and deaths. I’ll try to find the numbers reported from states that keep track of this. I read it in a medical blog I subscribe to.

Here is some data about breakthrough infections:

Michigan was among the first states to report numbers last week: 246 people who were fully vaccinated (more than 2 weeks out from their second dose) came down with COVID from January to March. Three of those people died.

Data from other states suggest similar low rates of breakthrough infection. Oregon, for instance, reported 168 cases of breakthrough infection among more than 700,000 fully vaccinated people as of April 2, with 19 hospitalizations and three deaths. Minnesota reported 89 cases among 800,000 fully vaccinated people as of March 22, with no deaths.

Other states that have reported breakthrough cases include Washington (102 cases, eight hospitalizations, two deaths among one million fully vaccinated); South Carolina (155 cases among more than 560,000 fully vaccinated); and Nevada (58 cases among more than 500,000 fully vaccinated).

So while its not common at all to get serious disease after vaccination it is happening. In the trials for the mRNA vaccines there was only a single case of severe disease and no deaths out of 30,000 people in the vaccinated groups. Now that millions of people are getting the mRNA vaccines we can see that very rarely people are dying despite being vaccinated. Not really surprising. I hope that all hospital admissions for covid are getting their virus sequenced-otherwise we don't know if one variant is more virulent than others.