mRNA and deviant proteins

2,525 Views | 14 Replies | Last: 3 yr ago by TheMasterplan
texan12
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Below article is from today. What are the ramifications of cells that are not effected by covid developing the spike protein? Is there a concern with competition with other mRNA already present in non-effected cells or cells in general? Would that be considered aberrant protein products the last article mentions?

https://medicalxpress.com/news/2021-10-toehold-rna-therapeutics-cell-therapies.html

"Delivering a synthetic RNA molecule into a cell essentially instructs it to produce a desired protein, which can then carry out therapeutic, diagnostic, and other functions. A key challenge for researchers has been to only allow cells causing or affected by a specific disease to express the protein and not others. This ability could significantly streamline production of the protein in the body and avoid unwanted side effects."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791314/

Published 2019

mRNA damage and disease

"In the previous sections, we discussed the susceptibility of RNA to damage and how it impacts the chemical properties and function of the molecule. Naturally, the next question is whether these alterations have any profound effect on organismal fitness. In this section, we discuss the connections between RNA damage and several disease states. Because an mRNA is translated multiple times, and in some cases more than a thousand times, a damaged mRNA has the potential of producing significant amounts of aberrant protein products. As defective protein products are more likely to misfold and aggregate, damaged mRNAs would pose significant challenges to tissues that are more sensitive to protein misfolding."
TXTransplant
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Both of those articles need to be read with the proper understanding of how mRNA is made and processed in the human body and the relationship between DNA and RNA.

The genes in DNA encode protein molecules.

In the simplest sense, expressing a gene means manufacturing its corresponding protein, and process has two major steps. In the first step, the information in DNA is transferred to a messenger RNA (mRNA) molecule by way of a process called transcription. During transcription, the DNA of a gene serves as a template for complementary base-pairing, and an enzyme called RNA polymerase II catalyzes the formation of a pre-mRNA molecule, which is then processed to form mature mRNA. The resulting mRNA is a single-stranded copy of the gene, which next must be translated into a protein molecule.

Link to this basic explanation here: https://www.nature.com/scitable/topicpage/translation-dna-to-mrna-to-protein-393/

You can't make mRNA without DNA. All mRNA is unstable and degrades easily. This is true of the mRNA in your body, as well as the mRNA in the vaccines. Bacterial mRNA has a half-life measured in minutes; mammalian mRNA can have a half-life of a day (see the paragraph under Figure 1 of the second article).

The vaccines only deliver enough mRNA to allow that mRNA to get into your cells and make enough spike protein to trigger an immunoresponse. Once your immune system identifies the cells with the spike protein, they are destroyed.

The mRNA from the vaccine does not stay in your body indefinitely, nor does it replicate.

The mRNA from the vaccine does not modify your DNA to produce more spike protein mRNA. For your body to make more spike protein than what can be made from the mRNA in the vaccine, your DNA would have to be genetically modified.

I know there are posters over on the politics board who like to say this isn't a vaccine, it's "gene therapy". That isn't true.

Gene therapy uses genes to treat disease. There are several approaches including
  • Replacing a mutated gene that causes disease with a healthy copy of the gene.
  • Inactivating, or "knocking out," a mutated gene that is functioning improperly.
  • Introducing a new gene into the body to help fight a disease.

Genes are made up of DNA - anywhere from a few hundred to a few million base pairs, depending on the gene. mRNA is NOT a gene.

Your body is constantly making mRNA and proteins. The mRNA damage being discussed in the second article is damage caused to mRNA caused by specific physiological conditions in the body, such as an excess of O2 in the cells, or the presence of certain chemicals in the body (like those from tobacco smoke) and chemotherapy drugs. Damage to mRNA due to the presence of these compounds occurs over time, not because of a single exposure.

That second article is more concerned with damage to the mRNA that your body makes as part of its normal operation, not any associated with the small amount of mRNA that might be injected as a vaccine.

While I'm no expert on RNA therapeutic technologies, in reading the first article, I think that's what it's really focused on. Remember, mRNA is being developed for more than just one-shot vaccines. Presumably, treating cancer with mRNA would involve more than just one or two shots. It would be a more long-term treatment.

However, it's important to understand that the very definition of a virus is that it hijacks your healthy cells and tells them to make more virus. Eventually, this destroys your healthy cells, killing them, or the virus can alter the DNA in your cells. The cells don't die, but they continue to replicate with the foreign virus DNA. There is evidence than certain viruses can mutate cells and cause them to become cancerous.

This process continues as long as your body is infected with the virus. Eventually, your immune system either kills all of the virus-containing cells, or you succumb to the virus and die. Or, in some cases, you can have an active virus that is dormant some of the time, but eventually does significant damage to the cells that you develop cancer (see the connection between HPV and cancer).

This is why having the covid virus itself is so much more dangerous than the vaccine. The virus will replicate over and over and over again, damaging more and more cells, until it is either killed or kills the host.

The mRNA vaccine injects a fixed amount of mRNA that produces a finite amount of spike protein. Your body attacks and destroys the cells with the spike protein, and any excess mRNA degrades. As I said earlier, this does not occur indefinitely, and there is no short or long-term change to your DNA (which, in turn means there is no long-term damage to your mRNA).

Edited to add: There are also several different types of RNA - mRNA, tRNA, and tRNA are the ones you hear about the most, and these three all participate in protein synthesis.

However, there are other types of RNA that can inhibit gene expression. These are the RNAs that play a role in cancer and other diseases. Since the first article uses the term "RNA", I don't think it is specific to only mRNA (although it does discuss mRNA). In fact, the article talks about using their "toehold switch systems" to alter gene expression, so more than just mRNA has to be involved.
texan12
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Thank you. The first article definitely needs clarification as it mentions the vaccine and synthetic RNA as if they are directly related to the mRNA vaccines. The second link was me going down a rabbit hole due to the first.

Do viruses typically only target certain cells, though? As far as your comment about viruses and cancer, could the asymptomatic infected still be fighting the virus months after infection and would getting the vaccine assist in stopping that infection?
TXTransplant
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I believe some viruses do only infect certain cells - think hepatitis C which attacks the liver. The virus can be detected in other places in your body, but it damages the cells in the liver.

This article talks about the different types of viruses, and mentions that the spike protein in covid has an affinity for the cells in the lungs.

https://www.google.com/amp/s/www.nbcnews.com/news/amp/ncna1202046

As far as covid is concerned, I don't know if it lies dormant. I haven't read anything that indicates it does.

I would expect the vaccine to be more effective in preventing subsequent infection rather than helping you fight off one that never really goes away.

Shingles is really just the chicken pox virus being reactivated after years of lying dormant. And the shingles vaccine will help prevent a shingles outbreak later in life.

But some antiviral drugs can also keep viruses dormant by binding with the viral proteins that have an affinity for healthy cells. This prevents the virus from entering the cells and replicating.

The thing is, viruses can be quite different. They are notoriously hard to prevent and cure - we've been successful with some, but think about ones like HIV, the flu, and even the common cold that we haven't been so successful in preventing and/or treating.

Antibiotics don't work in treating them. You can alleviate a patient's symptoms, but there is no "cure" for many - other than the body's immune system fighting it off.

Even antiviral drugs don't eliminate the virus - they just help your body fight the virus, prevent the virus from binding with cells, and help prevent spread by keeping viral counts low.

Viruses really aren't even alive until they hijack a healthy cell. So, you can't attack it until it invades a host cell - and you stop the virus by killing the host cell.
oldflyer
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AG
TXTransplant, thanks for the taking the time to explain this stuff. Its fascinating, but as a layman, it helps to have someone that can explain it on my level! Can I ask what you do? Sounds like you are in research of some type?
TXTransplant
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I'm a chemical engineer by degree. I have a PhD. My research area was in biofuels - specifically bacterial fermentations. So, I took classes in microbiology and biochemistry in addition to chemical engineering. I've written and reviewed many grant proposals and peer-reviewed journal publications, so I sort of "speak the language".

I had just started to look into genetic engineering of bacteria when I left academics and went to a start up company.

I'm out of the field entirely now (I'm a patent agent in the chemicals industry), but I still have a better than average understanding of this stuff.

Where my knowledge runs out is in human biology/physiology. I can make educated guesses, but I'm not an MD. So, I tread lightly when it comes to how viruses affect the human body, side effects of vaccines, etc.

I'll be honest - those two articles are a lot to digest for someone who isn't an expert. They made my head hurt. But I can pick through them enough to realize what they are discussing is different from the vaccines.
Rex Racer
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AG
TXTransplant said:

Both of those articles need to be read with the proper understanding of how mRNA is made and processed in the human body and the relationship between DNA and RNA.

The genes in DNA encode protein molecules.

In the simplest sense, expressing a gene means manufacturing its corresponding protein, and process has two major steps. In the first step, the information in DNA is transferred to a messenger RNA (mRNA) molecule by way of a process called transcription. During transcription, the DNA of a gene serves as a template for complementary base-pairing, and an enzyme called RNA polymerase II catalyzes the formation of a pre-mRNA molecule, which is then processed to form mature mRNA. The resulting mRNA is a single-stranded copy of the gene, which next must be translated into a protein molecule.

Link to this basic explanation here: https://www.nature.com/scitable/topicpage/translation-dna-to-mrna-to-protein-393/

You can't make mRNA without DNA. All mRNA is unstable and degrades easily. This is true of the mRNA in your body, as well as the mRNA in the vaccines. Bacterial mRNA has a half-life measured in minutes; mammalian mRNA can have a half-life of a day (see the paragraph under Figure 1 of the second article).

The vaccines only deliver enough mRNA to allow that mRNA to get into your cells and make enough spike protein to trigger an immunoresponse. Once your immune system identifies the cells with the spike protein, they are destroyed.

The mRNA from the vaccine does not stay in your body indefinitely, nor does it replicate.

The mRNA from the vaccine does not modify your DNA to produce more spike protein mRNA. For your body to make more spike protein than what can be made from the mRNA in the vaccine, your DNA would have to be genetically modified.

I know there are posters over on the politics board who like to say this isn't a vaccine, it's "gene therapy". That isn't true.

Gene therapy uses genes to treat disease. There are several approaches including
  • Replacing a mutated gene that causes disease with a healthy copy of the gene.
  • Inactivating, or "knocking out," a mutated gene that is functioning improperly.
  • Introducing a new gene into the body to help fight a disease.

Genes are made up of DNA - anywhere from a few hundred to a few million base pairs, depending on the gene. mRNA is NOT a gene.

Your body is constantly making mRNA and proteins. The mRNA damage being discussed in the second article is damage caused to mRNA caused by specific physiological conditions in the body, such as an excess of O2 in the cells, or the presence of certain chemicals in the body (like those from tobacco smoke) and chemotherapy drugs. Damage to mRNA due to the presence of these compounds occurs over time, not because of a single exposure.

That second article is more concerned with damage to the mRNA that your body makes as part of its normal operation, not any associated with the small amount of mRNA that might be injected as a vaccine.

While I'm no expert on RNA therapeutic technologies, in reading the first article, I think that's what it's really focused on. Remember, mRNA is being developed for more than just one-shot vaccines. Presumably, treating cancer with mRNA would involve more than just one or two shots. It would be a more long-term treatment.

However, it's important to understand that the very definition of a virus is that it hijacks your healthy cells and tells them to make more virus. Eventually, this destroys your healthy cells, killing them, or the virus can alter the DNA in your cells. The cells don't die, but they continue to replicate with the foreign virus DNA. There is evidence than certain viruses can mutate cells and cause them to become cancerous.

This process continues as long as your body is infected with the virus. Eventually, your immune system either kills all of the virus-containing cells, or you succumb to the virus and die. Or, in some cases, you can have an active virus that is dormant some of the time, but eventually does significant damage to the cells that you develop cancer (see the connection between HPV and cancer).

This is why having the covid virus itself is so much more dangerous than the vaccine. The virus will replicate over and over and over again, damaging more and more cells, until it is either killed or kills the host.

The mRNA vaccine injects a fixed amount of mRNA that produces a finite amount of spike protein. Your body attacks and destroys the cells with the spike protein, and any excess mRNA degrades. As I said earlier, this does not occur indefinitely, and there is no short or long-term change to your DNA (which, in turn means there is no long-term damage to your mRNA).

Edited to add: There are also several different types of RNA - mRNA, tRNA, and tRNA are the ones you hear about the most, and these three all participate in protein synthesis.

However, there are other types of RNA that can inhibit gene expression. These are the RNAs that play a role in cancer and other diseases. Since the first article uses the term "RNA", I don't think it is specific to only mRNA (although it does discuss mRNA). In fact, the article talks about using their "toehold switch systems" to alter gene expression, so more than just mRNA has to be involved.

Thank you for the clear explanation. I have a feeling vaccine adoption would be a lot more ubiquitous if the powers that be would have explained things like this instead of getting political.
texan12
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Ma'am, check this video out from a fellow PHD with an infectious disease background.



At about the 9 minute mark he describes the purpose of lipids in order to reach the cells and the follow up question concerns which cells it enters at the ~10 minute mark. He describes the majority enter muscular cells.
TXTransplant
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Yes, I'm somewhat familiar with the lipid nanoparticles. A colleague from my grad school and professor data (who was also a co-PI on an NSF grant that I received) has done a lot of work looking at the fate of nanoparticles in the environment and cells.

As the guy in the video said, lipids are just fat. At there are lipids in your cells. The lipid nanoparticles are the delivery vehicle for the mRNA.

I am not sure if you are concerned about the mRNA going into muscle cells. That's what going to happen with any vaccine that is delivered as a shot…some of the active ingredient (whether it's mRNA or a protein or a deactivated virus) will end up in muscle cells. But as he said, it does end up elsewhere, including immune cells.

And as I said before, the mRNA eventually degrades and your cells stop making the protein.

Edited to add: I was able to watch the entire video, and I think it's really good. I hope more people watch it.
Harry Stone
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AG
TXTransplant said:

Both of those articles need to be read with the proper understanding of how mRNA is made and processed in the human body and the relationship between DNA and RNA.

The genes in DNA encode protein molecules.

In the simplest sense, expressing a gene means manufacturing its corresponding protein, and process has two major steps. In the first step, the information in DNA is transferred to a messenger RNA (mRNA) molecule by way of a process called transcription. During transcription, the DNA of a gene serves as a template for complementary base-pairing, and an enzyme called RNA polymerase II catalyzes the formation of a pre-mRNA molecule, which is then processed to form mature mRNA. The resulting mRNA is a single-stranded copy of the gene, which next must be translated into a protein molecule.

Link to this basic explanation here: https://www.nature.com/scitable/topicpage/translation-dna-to-mrna-to-protein-393/

You can't make mRNA without DNA. All mRNA is unstable and degrades easily. This is true of the mRNA in your body, as well as the mRNA in the vaccines. Bacterial mRNA has a half-life measured in minutes; mammalian mRNA can have a half-life of a day (see the paragraph under Figure 1 of the second article).

The vaccines only deliver enough mRNA to allow that mRNA to get into your cells and make enough spike protein to trigger an immunoresponse. Once your immune system identifies the cells with the spike protein, they are destroyed.

The mRNA from the vaccine does not stay in your body indefinitely, nor does it replicate.

The mRNA from the vaccine does not modify your DNA to produce more spike protein mRNA. For your body to make more spike protein than what can be made from the mRNA in the vaccine, your DNA would have to be genetically modified.

I know there are posters over on the politics board who like to say this isn't a vaccine, it's "gene therapy". That isn't true.

Gene therapy uses genes to treat disease. There are several approaches including
  • Replacing a mutated gene that causes disease with a healthy copy of the gene.
  • Inactivating, or "knocking out," a mutated gene that is functioning improperly.
  • Introducing a new gene into the body to help fight a disease.

Genes are made up of DNA - anywhere from a few hundred to a few million base pairs, depending on the gene. mRNA is NOT a gene.

Your body is constantly making mRNA and proteins. The mRNA damage being discussed in the second article is damage caused to mRNA caused by specific physiological conditions in the body, such as an excess of O2 in the cells, or the presence of certain chemicals in the body (like those from tobacco smoke) and chemotherapy drugs. Damage to mRNA due to the presence of these compounds occurs over time, not because of a single exposure.

That second article is more concerned with damage to the mRNA that your body makes as part of its normal operation, not any associated with the small amount of mRNA that might be injected as a vaccine.

While I'm no expert on RNA therapeutic technologies, in reading the first article, I think that's what it's really focused on. Remember, mRNA is being developed for more than just one-shot vaccines. Presumably, treating cancer with mRNA would involve more than just one or two shots. It would be a more long-term treatment.

However, it's important to understand that the very definition of a virus is that it hijacks your healthy cells and tells them to make more virus. Eventually, this destroys your healthy cells, killing them, or the virus can alter the DNA in your cells. The cells don't die, but they continue to replicate with the foreign virus DNA. There is evidence than certain viruses can mutate cells and cause them to become cancerous.

This process continues as long as your body is infected with the virus. Eventually, your immune system either kills all of the virus-containing cells, or you succumb to the virus and die. Or, in some cases, you can have an active virus that is dormant some of the time, but eventually does significant damage to the cells that you develop cancer (see the connection between HPV and cancer).

This is why having the covid virus itself is so much more dangerous than the vaccine. The virus will replicate over and over and over again, damaging more and more cells, until it is either killed or kills the host.

The mRNA vaccine injects a fixed amount of mRNA that produces a finite amount of spike protein. Your body attacks and destroys the cells with the spike protein, and any excess mRNA degrades. As I said earlier, this does not occur indefinitely, and there is no short or long-term change to your DNA (which, in turn means there is no long-term damage to your mRNA).

Edited to add: There are also several different types of RNA - mRNA, tRNA, and tRNA are the ones you hear about the most, and these three all participate in protein synthesis.

However, there are other types of RNA that can inhibit gene expression. These are the RNAs that play a role in cancer and other diseases. Since the first article uses the term "RNA", I don't think it is specific to only mRNA (although it does discuss mRNA). In fact, the article talks about using their "toehold switch systems" to alter gene expression, so more than just mRNA has to be involved.


I write about it a little in this thread

https://texags.com/forums/84/topics/3235972/replies/60432540#60432540

The first article is a way to target my concerns with targeting specific cells
TXTransplant
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Interesting points.

I haven't given the cell issue too much thought, and here's why (it's the engineer in me):

The human body is made up of an estimated 37 trillion cells. And the body is constantly making new cells, both to grow and to replace those that die.

The amount of mRNA in a vaccine is incredible small compared to the total number of cells.

So, even if the vaccine does target the "wrong" cells or even if it disrupts normal cellular pathways, it's in such a small amount compared to your total number of cells that it's hard to imagine it causing major issues. And it still wouldn't be expected to cause long-term issues because the mRNA doesn't stick around for more than a few days.

In my word, we say "Dilution is the solution to pollution". That kind of applies here - the body's "normal" cells are always going to vastly outnumber any that are affected by the short-term effects of the vaccine.

Seems like a misplaced concern, but again, I'm not an MD. And I'm applying my engineering expertise to a medical/health problem.

But, with that said, I don't think widespread vaccination of children is necessary. Not because of any concerns I have with the vaccines but because the data literally shows it's not necessary. This virus is not life-threatening to the vast majority of healthy kids.
TheMasterplan
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I think TXTransplant is my favorite poster on TexAgs. Academic but not socially ******ed so she knows how to talk to people.

My favorite posts were she told everyone she was talking fitness classes and everyone got offended about her possibly risking COVID for everybody.
TXTransplant
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Ha! Thanks for the compliment. My students didn't appreciate me that much when I was a prof!

You have a great memory! That post was about a year ago. Maybe more. And yeah, there was one person in my family who was very upset that I was going to my group fitness class and then going to work and sending my son to school. That was back before the vaccine.
texan12
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Your info is incredibly valuable and I have been reading your previous posts for the past hour. I haven't seen such clear explanations. My concerns are now not focusing so much on vaccine long-term effects since there are only finite proteins produced and trillions of cells.

I've always justified the necessity for the vaccine based of your chances of hospitalization. As simple as it gets obviously. But the chances of infection, even though I'm not worried about the virus short term, seems as if those long term effects should be more concerning. Infinite (maybe) proteins produced and a virus potentially damaging our dna is no bull *****

TXTransplant
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Thanks! I do want to clarify for anyone reading that my posts above don't state that Covid causes long term damage to your cells/DNA that could cause cancer. I haven't read any evidence of that.

However, there are other viruses that do this (ie, HPV). I was just trying to explain how viruses in general can behave in the human body and why they can be so dangerous and hard to cure and/or vaccinate against. And the risk of long term effects varies from virus to virus, and even person to person (depending on your immune system).

But the risks of the covid vaccine (or any vaccine for that matter) causing any severe adverse effects, either short or long term, is much less than the risk of adverse effects from an infection by the actual virus.
TheMasterplan
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TXTransplant said:

Ha! Thanks for the compliment. My students didn't appreciate me that much when I was a prof!

You have a great memory! That post was about a year ago. Maybe more. And yeah, there was one person in my family who was very upset that I was going to my group fitness class and then going to work and sending my son to school. That was back before the vaccine.
I know but I liked that you evaluated the risk but thought it was ridiculous that you couldn't continue to stay in shape for your general health. There has to be some semblance of normality.

I have also enjoyed our discussion around "modern feminism" and engineering and how they relate.
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