What I think is missing in the discussions of the modRNA platform

Some concepts to consider and understand that are often not talked about

Sometimes when I scroll on Twitter or read articles on these modRNA vaccines, I feel certain very important principles are often glossed over or not understood. Now I may be completely wrong on these concepts, but I will present them in the hopes of being corrected or have my knowledge expanded.

modified mRNA

We should always keep in mind that these mRNAs are biosynthetic and are significantly modified from the viral mRNA. This term, is mostly applied to the N-1-methylpseudouridine substitution. This changes a great deal of biochemistry and just as importantly how we measure the modRNA and ensure its purity. Kevin McKernan has covered this quite extensively. So here are some of the issues identified (are there more?)

1. frameshifting

2. DNA/RNA hybrids

3. virioid like mRNA

4. friend or foe? see Doorless Carp or friend or foe

Engineered mRNA

David Wiseman and I like this term because it encompasses all the OTHER changes to the mRNA including codon optimization, changes to the poly (A) tail, stop codons, the human 3’ UTR etc. Some of these changes have significant effects on the resulting spike protein. see Consequences of mRNA modifications. This should have stopped the whole mRNA train, in and of, itself.

1. aberrant folding (risks of toxicity)

2. changes in glycosolation and thus changes in immunity and antibody formation

3. possible chimeric proteins and autoimmunity

Pro-Drug (ie pro-vaccine) and the Pharmacologic Phase

Pro-drugs are those that are converted intracellularly either by therapeutic target cells (Type IA) or (Type IB) by metabolic tissues (e.g., liver, gut). The inactive pro-drug molecule undergoes a direct biochemical reaction to produce the active drug form.

This is what happens with the mRNA (pro-drug). It gets biologically converted to the spike protein. No antigen is administered, it is the mRNA that is converted to the spike protein. Therefore it is not a vaccine like any other. A different mechanism of action.

So for pro-drugs, the pro-drug itself (ie the mRNA) may contribute to the overall safety and toxicity profile of the active drug. How much and how fast does a pro-drug converts to the active drug format? How much remains intact in the body? What about the modRNA impurities, including truncated and fragmented modRNA? Does this contribute to the overall toxicity profile? This is usually taken into account for regulatory approval of pro-drugs. But not so in this case because this pharmacological phase was ignored into vaccine guidance.

You can make this case without having to resort to “its a gene therapy product” though of course it is. So refer to it as a pro-vaccine.

Biocorona

Not well known and not talked about enough. The biocorona on the LNPs gives it a biological identity and STEALTH properties. The body does not recognize the synthetic mRNA or the synthetic LNPs because the LNPs are covered with our OWN proteins (which are individualized for each person). So they can go throughout the body in STEALTH mode. I talk about the biocorona in this substack entry

Bio distribution part 1

CARPA

I really need to do a substack on this alone, but pegylated nanoparticles are known to cause an allergic type reaction, or anaphylactoid reaction called Complement Activated-Reaction Pseudoallergy. It can be quite serious and it can be fatal. Assessment for the risk of CARPA is required for all pegylated drugs, but of course wasnt done for these jabs. Likely because Pfizer hand waved it away by saying the jabs are given IM and the quantity is so small. BUT this new article blows that explanation out of the water. Brilliant work Dr Szebeni!

CARPA IS HUGE!. The risk is 5 times higher than with pegylated doxorubicin, chemotherapy given for breast cancer. I believe that studying complement activation can explain many adverse events of these jabs, including complement damage to organs. Plus there are potential therapeutic options. More later.

mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions

Transfection

This concept along with pro-vaccine are crucial to understand. This took me a while too and I struggled to explain the concept and HOW DIFFERENT it is from all other therapeutics administered until these jabs.

Drugs and even monoclonal antibodies (ligands) work through RECEPTORS on the cell phospholipid membrane.

Pharmacology 101 Pharmacology Education Project

Although the ligands of interest to prescribers are exogenous compounds (i.e. drugs), receptors in human tissues have evolved to bind endogenous ligands such as neurotransmitters, hormones, and growth factors. Formation of the drug-receptor complex is usually reversible and the proportion of receptors occupied (and thus the response) is directly related to the concentration of the drug. Reversibility enables biological responses to be modulated and means that similar ligands may compete for access to the receptor. The term 'receptor' is usually restricted to describing proteins whose only function is to bind a ligand, but it is sometimes used more widely in pharmacology to include other kinds of drug target such as voltage-sensitive ion channels, enzymes and transporter proteins.

So the ligand/receptor complex is usually reversible allowing for modulation. So the cell can respond to the ligand as required, and there are often several subtypes specific for certain actions. A very specific, responsive system. It is worthwhile reading about a nuclear receptor that modulates bile acids. A very delicate finely tuned system for a molecule made by our bodies. Subtypes, specificity, expression is certain tissues, etc etc.

But transfection is different. It is chemically based molecules that break open the cell wall. It is brute force transversing the sensitive phospholipid membrane with a stealth nanoparticle, that once inside the cell, exposes itself as a biosynthetic nucleic acid and lipids. Or as a knife cutting through as Things Hiddenn says. No warning, no modulation, no ability to limit entry, etc etc. Like a Trojan horse. Since the LNP has a biocorona it is the same size, shape and coated with lipoproteins and looks just like small cholesterol molecule, a chylomicron. But since it is not what is expected, this sets off a whole bunch of biochemical responses, cross talk etc in the cell. The kind of stuff Narf was talking about on X and also Dr Bines. I am very bad at this protein stuff and detail, but I believe that the whole concept of transfection is in itself dangerous, even if the mRNA is not codon optimized, and even (though markedly less), if it is non-coding RNA.

So we really need to understand transfection and provide a way of conveying this concept so everyone understands how DIFFERENT AND UNKNOWN this is. Anyone who can help in this endeavor? Comparing MOA of drugs vs mRNA transfections?

"Shedding”

Shedding will always occur with a gene therapy product and this has been known for a long time. Shedding occurs via exosomes and not, as many say, through active virus “shedding”. I really dont think we should call it shedding. It needs a new name.

Helen Banoun wrote about this concept earlier and has been vindicated. Banoun

Also read Siguna Miller’s extensively researched paper on the environmental risk of shedding with the COVID-19 vaccines. Siguna Mueller

The Process is the Product

Why is the manufacturing of the mRNA SOOOO IMPORTANT? Because each time you manufacture it you can get a slightly different product. And in biology that it critically important.

I cover that here:

When you think about Process 1 vs Process 2 manufacturing, plus every site making these jabs is really another Process, the variability of the jabs is huge. It makes my head hurt.

Summary

I feel we need to talk more about:

1. modRNA or engineered RNA or my favorite “plastic RNA” instead of mRNA

2. pro-vaccine instead of vaccine (I know I know, but legally it is a vaccine)

3. transfection

4. shedding

5. CARPA

6. the process is the product

and less on antibodies, schmantibodies to the true nature of these jabs. But I admit I am biased.

Thanks for reading and pray the rosary