Thread by @eh_den

REVERSE ENGINEERING: WHAT DO WE KNOW ABOUT THE GENETIC CODE WITHIN THE PFIZER VACCINE?

(thread)
What does the mRNA code in the Pfizer vaccine tell us about the genetic design decisions, its safety, possible impact on our health, and the "quality" of FDA BLA approval?

#COptiGate

This is going to be A LONG thread; I will review the code after the introduction. As usual (with my posts), please use the "show replies" option multiple times to unveil the whole thread.

OK, let's start!

#COptiGate

The FDA's approval to Pfizer'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 ???

#COptiGate

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" in order to get the context; use "show replies" to expand the thread.

#COptiGate

https://twitter.com/eh_den/status/1426885632140394499

The wonder of the mRNA vaccine (which was invented by @RWMaloneMD) 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.

#COptiGate

This leads us to two important questions:
1) What is that code?
2) 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?

#COptiGate

As I've written in the past, Pfizer, 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.

#COptiGate

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.

#COptiGate

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 mRNA code was designed as a case example to the risks both the FDA & Pfizer has chosen to ignore.

#COptiGate

https://twitter.com/eh_den/status/1427352028616044548

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.

#COptiGate

berthub.eu/articles/posts…

Kira Smith published a paper pointing out problems within the genetic code of the Pfizer vaccines ("BNT162b2 Vaccine: possible codons misreading, errors in protein synthesis and alternative splicing's anomalies", March 2021)

doi.org/10.22541/au.16…

#COptiGate

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)

senseofawareness.com/2021/08/20/cop…

#COptiGate

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" ???

mdpi.com/journal/vaccin…
#COptiGate

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."

dx.doi.org/10.3390%2Fvacc…
#COptiGate

Professor Xia's paper covers both the Moderna and Pfizer mRNA products, and in this thread I will be focusing only on his review of the Pfizer product.

My purpose is to allow you to understand how design decisions impact product safety, how it can impact your health.

#COptiGate

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"

#COptiGate
dx.doi.org/10.3390%2Fv130…

FINALLY, CODE REVIEW !!!
#COptiGate

The protein created by the Pfizer 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.

#COptiGate

1) S-2P is an unstable protein.
2) 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)
doi.org/10.1038/s41467…
#COptiGate

Because our cell attacks foreign genetic code, The Pfizer mRNA code replaced all the U letters (nucleotides) in it with Ψ letters to hide itself, which increases the probability of misreading the code and generating a different spike protein than what was expected.

#COptiGate

At the end of the Pfizer 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.

#COptiGate

Since mRNA optimization is based on highly expressed protein coding genes, and since the the Pfizer vaccine is "administered through muscle injection, it is relevant to characterize features of highly expressed muscle genes."

#COptiGate

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"

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.
#COptiGate

PLEASE DO NOT RETWEET YET!

Much more to come below...
If you arrived here and there is nothing yet... PLEASE COME BACK.

Press the "Show replies" to see the rest of the thread.
"Show replies"
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#COptiGate

WELCOME TO SECTION 2:

As you can see below, in the Arg residues (R) ribosomal protein genes, the Pfizer product has reduced AGR codons by 8 while increasing the corresponding CGN codons by the same amount (compared to the original SARS_CoV_2).

#COptiGate

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.

#COptiGate

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.

#COptiGate

The 2nd level of optimization is done within a family, where a fundamentalist strategy was taken. As you can see, Pfizer chose "CGG as the optimal codon in the CGN codon family and recorded almost all CGN codons to CGG".

#COptiGate

They did so because:

1) The codon compilation of human genes in EMBOSS showed that CGG is slightly more frequent than CGC.
2) We have 4 tRNA genes to decode CGG, and 6 tRNA to decode CGA and CGG.

#COptiGate

However:
1) EMBOSS was created in 1993-1994 and did not focus on highly expressed protein coding genes.
2) "Nearly half of human tRNA genes are not expressed"

The better codon to use was CGC. "THE DESIGNERS OF THE VACCINES,..CHOSE A WRONG CODON AS THE OPTIMAL CODON."

#COptiGate

More 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.

#COptiGate

"The codon optimization...leads to a much increased codon adaptation index (CAI) and index of translation efficiency (ITE)"

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.

@XuhuaX 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?

#COptiGate

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.

#COptiGate

However, there could be cases when poor codon adaptation and variable sites are associated but not related to translation accuracy.

#COptiGate

According to @XuhuaX, there are two approaches to optimization:

1) Choose a codon with an empirically defined lowest error rare (Pfizer way).

2) Choose codons that are used in functionally important and highly expressed genes.

If #2 was used, CGC would be chosen.

#COptiGate

"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"

GOptiGate

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.
#COptiGate

The Kozak consensus is a sequence that enhances the translation initiation. For mammalian genes it is GCCRCCAUGG, where AUG is the start codon."

Pfizer uses GCCACCAUG, but not the codon after that, to prevent unpredictable changes in the spike protein.

#COptiGate

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".

#COptiGate

Pfizer has chosen human α-globin as their 5'-UTR, with minor modifications to the Kozak consensus.

Translation Termination Signal:
Pfizer 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 termination signal may not be the optimal choice."

#COptiGate

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... vaccines COULD BE EVEN WORSE"

#COptiGate

"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."

#COptiGate
rnajournal.cshlp.org/content/10/4/6…

Tetranucleotide Termination Signal:
"the optimal stop signal should be UAAA instead of UGAU/UAGU/UAAU in the two mRNA vaccines."

Because Pfizer has changed all the U letters to Ψ, the stop signal in Pfizer 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.

#COptiGate

The 3'-UTR:

Pfizer'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.

Conclusions, etc...SOON!!!

#COptiGate
(Remember: Show replies)
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Before we continue:
@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 pointed out, that the 2P change is the use of Pseudouridine (2P) can create translation errors in the ribosome.

#COptiGate
pnas.org/content/116/46…

And as someone just sent me, @RWMaloneMD published a research paper that shows the dangers of frameshifted protein translation, which was described as a real concern in @XuhuaX paper.

@COptiGate

https://twitter.com/PleiadesTaygeta/status/1431787783681679365

1) The S-2P spike protein is not training correctly the body's immune system
2) mRNA not optimized correctly
3) mRNA not optimized for accuracy, lead to creation of different proteins
4) mRNA Can generate harming longer proteins

Plus read the abstract.

#COptiGate

The FDA had no concerns.

NO CONCERNS ? REALLY?

HOW THE HELL does Pfizer 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, 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 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.

People are terrified to see the truth, like I was terrified to see it.

https://twitter.com/eh_den/status/1430868765378498562

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.

Please join us at T.ME/EH_DEN
❤️
Ehden

CODON OPTIMIZATION - VIDEO EDITION 1/2

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.

Link to the full interview:
rumble.com/vlbebv-the-cou…

#CoptiGate

CODON OPTIMIZATION - VIDEO EDITION 2/2

Here's the 2nd clip from the interview I had with Tina Griffin from The Counter Culture Mom Show, about the level of regulatory oversight on these experimental gene therapies.

Link to the full interview:
rumble.com/vlbebv-the-cou…

#COptiGate