#COptiGate - Reverse Engineering (EXPANDED)
What does the mRNA code in the Pfizer/BioNTech vaccine tell us about the genetic design decisions, its safety, possible impact on our health, and the "quality" of FDA BLA approval?
AUTHOR COMMENTS FOR THE 2024 EDITION
What you are about to read is an article that published on the 29th of October 2021, which was the 3rd in a series I’ve written on the risks related to the use of Codon Optimization. The first article in the series was entitled “COPTIGATE - THE WORST DESIGN FLAW IN HUMAN HISTORY THAT IS IMPACTING YOUR HEALTH”. The second article was entitled “COPTIGATE - 3D CHESS EDITION”. I’ve combined them to one Substack post which you can find HERE. It is a long article but it had to be, because I tried to make the information discussed as accessible as possible.
SINCE X/TWITTER IS CENSORING MY CONTENT, I HAVE DECIDED TO RE-PUBLISH THE INFORMATION HERE. IT IS AS RELEVANT TODAY AS IT WAS WHEN IT WAS PUBLISHED IN 2021! Frameshifting, lack of optimization for accuracy, bad design that lead to leaky termination, the problems of using N1-Methylpseudouridine - ALL OF IT WAS KNOWN!
Early code analysis
The FDA's approval to Pfizer/BioNTech's Biological License Application (BLA) stated "...our review of information submitted in your BLA application...did not raise concerns or controversial issues that would have benefited from an advisory committee discussion."
REALLY ???
This thread is a follow up to previous threads I've written. I highly recommend reading "COPTIGATE - THE WORST DESIGN FLAW IN HUMAN HISTORY THAT IS IMPACTING YOUR HEALTH".
The wonder of the mRNA vaccine (which was invented by Dr Robert Malone
) is that it allows us to use our cell's own mechanisms of generating proteins (ribosomes etc.) to generate the proteins we wish, by using a genetic code encapsulated in a lipid.This leads us to two important questions:
What is that code?
What does it produce?
We have been told that the mRNA vaccine generates the spike protein of the original SARS_CoV_2 virus, and this trains our bodies to develop antibodies to the spike protein. IS IT?
As I've written in the past, Pfizer/BioNTech, Moderna, Janssen, and AstraZeneca all use Codon Optimization (CO) techniques in order to find a way to generate large amount of spike proteins with the intention of "training" your body to recognize the virus when it will see it.
It was known to manufacturers and regulators (since 2011) that CO is an issue, but since all the manufacturers got an exemption from submitting their products as gene therapy treatment and went via the normal vaccine process it was not checked as part of the approval.
Because "refusal to measure risk IS ALWAYS an indication that someone knows there is a real problem", let us look at the way the Pfizer/BioNTech mRNA code was designed as a case example to the risks both the FDA & Pfizer/BioNTech has chosen to ignore.
In December 2020 Bert Hubert wrote an excellent article called "Reverse Engineering the source code of the BioNTech/Pfizer SARS-CoV-2 Vaccine", and in it he explained (to mortals like us who are not geneticist) the mRNA code structure.
Kira Smith published a paper pointing out problems within the genetic code of the Pfizer/BioNTech vaccines ("BNT162b2 Vaccine: possible codons misreading, errors in protein synthesis and alternative splicing's anomalies", March 2021)
HOWEVER, I received a feedback from some "scientist" who "explained" to one of my readers that they should ONLY listen to scientists & MD who are experts in their field, and not to … (multiple personal insults toward me & Kira Smith lol)
So, how about a paper published in an international, peer-reviewed, open access journal monthly online by MDPI, which is affiliated with The American Society for Virology (ASV)?
Is that good enough for you, "Fact Checkers" ???
VaccinesVaccines, an international, peer-reviewed Open Access journal.https://www.mdpi.com/journal/vaccines
The Xia Code Review
Professor Xuhua Xia (@XuhuaX), an evolutionary biologist who work in the University of Ottawa (11696 Citations), published in vaccines (Jul 2021) "Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines."
Professor Xia's paper covers both the Moderna and Pfizer/BioNTech mRNA products, and in this thread I will be focusing only on his review of the Pfizer/BioNTech product. My purpose is to allow you to understand how design decisions impact product safety, how it can impact your health.
Before we dive, if you want to understand what might have impacted the decision making of designing this product, pls see @XuhuaX's previous paper:
"Domains and Functions of Spike Protein in SARS_Cov_2 in the Context of Vaccine Design"
FINALLY, CODE REVIEW !!!
The protein created by the Pfizer/BioNTech vaccine IS different from the spike protein of the original SARS-CoV-2, to try and stabilize the resulting spike protein.
The protein carrying these substitutions and additional furin site mutations is known as S-2P.
S-2P is an unstable protein.
S-2P's receptor binding domains (RDBs) are in an up (open) state, which doesn't train the body correctly as the original spike RDBs are closed.
("Stabilizing the closed SARS-CoV-2 spike trimer", Nature, 2021)
Because our cell attacks foreign genetic code, The Pfizer/BioNTech mRNA code replaced all the U letters (nucleotides) in it with Ψ letters (N1-Methylpseudouridine, which you can read more about in my article “deadly substitution”) to hide itself, which increases the probability of misreading the code and generating a different spike protein than what was expected.
At the end of the Pfizer/BioNTech mRNA there is a codon (3 letters) which acts like a stop signal. However, U in stop codons was replaced by Ψ, which increase the probability of either not generating the spike protein OR generating a longer protein with a harming effect.
Since mRNA optimization is based on highly expressed protein coding genes, and since the the Pfizer/BioNTech vaccine is "administered through muscle injection, it is relevant to characterize features of highly expressed muscle genes."
Because the muscle cells barely have any antiviral protein called ZAP, it suggests that the "spike mRNAs in the vaccine injected into muscle cells will not be subject to ZAP-mediated RNA degradation"
Codon Optimization, Level 1
The 1st level of codon optimization is done on codon families: there are 'CGN' codons (CGA, CGC, CGG, CGU) and there are 'AGR' codons (AGG, AGA). Most of the SARS_CoV_2 virus is encoded by AGR codons to avoid the antiviral ZAP proteins which target foreign CGN codons.
As you can see below, in the Arg residues (R) ribosomal protein genes, the Pfizer/BioNTech product has reduced AGR codons by 8 while increasing the corresponding CGN codons by the same amount (compared to the original SARS_CoV_2).
The compound codon family for Leu (L) optimization is similar: the UUR codons (UUA & UUG) have been completely replaced by CUG, and almost all of the CUA, CUC, and CUU codons have been replaced by CUG.
With the compound codon family for Ser (S), AGU is preferred, even for most of the UCN subfamily (UCA, UCC, UCG, UCU), for various reasons.
As a comparison, notice how in Moderna almost all of the compound codon family for Ser has been coded with AGU.
Codon Optimization - Level 2
The 2nd level of optimization is done within a family, where a fundamentalist strategy was taken. As you can see, Pfizer/BioNTech chose "CGG as the optimal codon in the CGN codon family and recorded almost all CGN codons to CGG".
They did so because:
The codon compilation of human genes in EMBOSS showed that CGG is slightly more frequent than CGC.
We have 4 tRNA genes to decode CGG, and 6 tRNA to decode CGA and CGG.
However:
EMBOSS was created in 1993-1994 and did not focus on highly expressed protein coding genes.
“Nearly half of human tRNA genes are not expressed"
Pfizer/BioNTech used wrong codons!
The better codon to use was CGC. "THE DESIGNERS OF THE VACCINES,..CHOSE A WRONG CODON AS THE OPTIMAL CODON."
More Codon Optimization
Ribosomal protein genes favor G-ending codons in every 2-fold R-ending codon family; C-ending codon is the optimal codon for 2-fold Y-ending codons family, and U-ending codons recorded to C-ending codons to prevent wobbling.
"The codon optimization...leads to a much increased codon adaptation index (CAI) and index of translation efficiency (ITE)"
Codon were NOT optimized for accuracy
however...
"THE CODON OPTIMIZATION IN THE PREVIOUS SECTION SUFFERS FROM LACK OF CONSIDERATION FOR TRANSLATION ACCURACY", because it has not taken into account the misreading rate.
Xia gives an example of E. coli, where AAC is heavily used, and AAU is rarely used.
The tRNA misreads AAC and AAU, and the misreading error rate is six times greater for AAU than for AAC.
Is the optimization for increased efficiency, or accuracy, or both?
One theory to identify if optimization is for increased efficiency, accuracy, both is by looking at the sites optimized. If optimization is for accuracy, conserved sites (functional) and variable sites (limited functionality) will be optimized differently.
However, there could be cases when poor codon adaptation and variable sites are associated but not related to translation accuracy.
According to @XuhuaX, there are two approaches to optimization:
Choose a codon with an empirically defined lowest error rare (Pfizer/BioNTech way).
Choose codons that are used in functionally important and highly expressed genes.
If #2 was used, CGC would be chosen.
"IT IS IMPORTANT FOR VACCINE mRNA TO BE TRANSLATED ACCURATELY BECAUSE MISINCORPORATION OF THE WRONG AMINO ACIDS WOULD CONFUSE OUR IMMUNE SYSTEM IN TARGET RECOGNITION"
Translation Initiation Sequence
After we looked at the optimization, let us look at other elements of the mRNA code, such as the translation initiation sequence, which is important because it can limit the rate of translation, and it depends on The Kozak consensus sequence, and a secondary structure.
The Kozak consensus is a sequence that enhances the translation initiation. For mammalian genes it is GCCRCCAUGG, where AUG is the start codon."
Pfizer/BioNTech uses GCCACCAUG, but not the codon after that, to prevent unpredictable changes in the spike protein.
Next in line, the 5'-UTR. The genetic code starts with a 5'-UTR area and ends with the 3'-UTR. 5'-UTR serves two key functions: to stabilize mRNA and to facilitate scanning by small ribosome subunit to localize the start codon".
Pfizer/BioNTech has chosen human α-globin as their 5'-UTR, with minor modifications to the Kozak consensus.
Translation Termination Signal
Pfizer/BioNTech uses two UGA stop codons (UGAUGA). "studies suggest that UAA...is more efficient than other stop signals", and "UGA is the leakiest" when it comes to accuracy.
"The Pfizer(/BioNTech) termination signal may not be the optimal choice."
Because there is a possibility of a frameshift (bad reading), where due to read error the stop codon will not be recognized, "UGA is a poor choice of a stop codon, and (THE) UGAU (due to the UGAUGA sequence) in PFIZER(/BioNTech)... vaccines COULD BE EVEN WORSE"
"The efficiency of translation termination is primarily determined by a tetranucleotide termination signal consisting of the stop codon and the first nucleotide immediately 3' of the stop codon." (“Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae”, Keeping at al, 2004)
This means that "the optimal stop signal (Tetranucleotide Termination Signal) should be UAAA instead of UGAU/UAGU/UAAU in the two mRNA vaccines."
FRAMESHIFTING
Because Pfizer/BioNTech has changed all the U letters to Ψ, the stop signal in Pfizer/BioNTech is ΨGAΨGA. As Ψ can pair with A,G (and less extent to C and U), it is more prone to misreading, and since UGAU can lead to a frameshift, ΨGAΨ may do the same.
The 3'-UTR
Pfizer/BioNTech's 3'-UTR is combined of a human AES/TLE5 segment of 136 nt with two CΨY mutation + 139 nt of a human mitochondrial 12S rRNA (mtRNR1), a combination of SELEX and borrowing from nature.
Nothing to see here, I’m sure!
Conclusions
FIRST - @XuhuaX deserves our respect and gratitude for the phenomenal work he has done. THANK YOU Xuhua Xia !!!
So... what did we learn today?
We already knew, as Kevin McKernan (
Also, Dr Malone published a research paper that shows the dangers of frameshifted protein translation, which was described as a real concern in @XuhuaX paper. Remember:
The S-2P spike protein is not training correctly the body's immune system
mRNA not optimized correctly
mRNA not optimized for accuracy, lead to creation of different proteins
mRNA Can generate harming longer proteins
For closure, I invite you to read the abstract of Xia’s paper I’ve reviewed in great details:
THE FDA
The FDA had no concerns.
NO CONCERNS ? REALLY?
HOW THE HELL does Pfizer/BioNTech get from the FDA approval for a Biologics License Application of a gene therapy which is NOT optimized for accuracy and has so many flaws?
I'll tell you how: THEY NEVER REALLY CHECKED IT.
Ignorance is bliss for Pfizer/BioNTech, who gets to make HUGE profits from shipping a product with so many design flaws that if it was a car it would have been recalled faster than you can say Jack Robinson.
Ignorance is bliss for the FDA who isn't really held accountable for anything.
Ignorance is NOT a bliss to everyone who trusted our medical regulators.
NOT EVEN ONE REGULATOR across the globe has looked at this Pfizer/BioNTech product as a gene therapy. NOT EVEN ONE.
Yesterday I realized why people hang on to the dream that they can get their pre-COVID life back. They hang on to this dream, like I hang on to my dream I can have my life back.
BONUS - The Tina Interview
Here is the 1st clip from the interview I had with Tina Griffin from The Counter Culture Mom Show, in it I summarize the topic of Codon Optimization.
PART 1:
PART 2:
FINAL WORDS
People are terrified to see the truth, like I was terrified to see it.
The Egyptians had the Egyptian book of the dead.
The Tibetan had the Tibetan book of the dead.
It is time for us to have a COVID BOOK OF THE DEAD.
COVID has killed the life YOU had, but YOU ARE NOT ALONE.
WE ARE ONE.
❤️
Ehden
"Because our cell attacks foreign genetic code.... "
Seems like the entire notion of transfection should end right here. Human bodies do not tolerate foreign proteins, not even when the treatment is designed to correct a defective gene as we learned in 1999 with the case of Jesse Gelsinger. Human biology has not changed only the hubris and faith in models that conclude humans can augment the immune system w mRNA transfection.
https://timothywiney.substack.com/p/could-altered-hydrophobicity-explain