A Closer Look at N1-methylpseudouridine in the Modified mRNA Injectables

Authors

  • Daniel Santiago Pharmacist in Florida

DOI:

https://doi.org/10.56098/5azda593

Keywords:

modified mRNA spike coding sequence, N1-methylpseudouridine, pseudouridine, SARS-CoV-2 spike coding sequence

Abstract

Introducing 728 N1-methylpseudouridines into the spike coding sequence for SARS-CoV-2 has inevitably resulted in physical changes in the original SARS-CoV-2 coding sequence. These non-negligible physical changes include: (1) stereochemical alterations; (2) variations in molecular weight; and (3) changes in the nucleotide base count consisting of A, G, T(U, Ψ), C. Assuming only that things are going as planned by the inventors of the new technology, the physical changes in each of the 728 substitutions in the SARS-CoV-2 spike coding sequence, where a uridine is replaced with an N1-methylpseudouridine, engages the ribosome as it reads, interprets, and translates the modified mRNA spike coding sequence into a specific sequence of amino acids. Whatever the peptide/protein sequence turns out to be must set up a cascading series of downstream consequences from whatever adjustments occur in the largely unpredictable peptide/protein sequences being produced by the ribosome. The stereoscopic changes in moving from uridine to pseudouridine involve rotating the uracil ring structure 180º and shifting three carbon positions clockwise; then, the further modification of pseudouridine to N1-methylpseudouridine involves the introduction of a methyl group leading to even more noticeable changes in the stereochemical configuration. I also document physical changes in molecular weight and in base count. Such physical modifications must have cascading effects on interactions across all levels of the downstream peptide/protein products produced from the never before encountered sequences of nucleotides. Given such physical modifications, can the proteinaceous materials produced by the modified mRNA coding sequences lead to the production of effective antibodies against the SARS-CoV-2 spike protein? What can be expected from repeated exposures to these foreign modified mRNA sequences through multiple doses and subsequent booster injections? Empirical outcomes, it seems, get worse with each new dose rather than better.

Author Biography

References

A Midwestern Doctor. (2023, January 18). Do the mysterious fibrous clots really exist? The Forgotten Side of Medicine. https://www.midwesterndoctor.com/p/do-the-mysterious-fibrous-clots-really

Adizie, T., & Adebajo, A. O. (2014). Travel- and immigration-related problems in rheumatology. Best Practice & Research Clinical Rheumatology, 28(6), 973–985. https://doi.org/10.1016/j.berh.2015.04.006

Aldén, M., Olofsson Falla, F., Yang, D., Barghouth, M., Luan, C., Rasmussen, M., & De Marinis, Y. (2022). Intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 in vitro in human liver cell line. Current Issues in Molecular Biology, 44(3), 1115–1126. https://doi.org/10.3390/cimb44030073

Bansal, S., Perincheri, S., Fleming, T., Poulson, C., Tiffany, B., Bremner, R. M., & Mohanakumar, T. (2021). Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines. Journal of Immunology (Baltimore, Md.: 1950), 207(10), 2405–2410. https://doi.org/10.4049/jimmunol.2100637

Bradley, C. C., Gordon, A. J. E., Wang, C., Cooke, M. B., Kohrn, B. F., Kennedy, S. R., Lichtarge, O., Ronca, S. E., & Herman, C. (2022). RNA polymerase inaccuracy underlies SARS-CoV-2 variants and vaccine heterogeneity. Research Square, rs.3.rs-1690086. https://doi.org/10.21203/rs.3.rs-1690086/v1

Bradley, C. C., Wang, C., Gordon, A. J. E., Wen, A. X., Luna, P. N., Cooke, M. B., Kohrn, B. F., Kennedy, S. R., Avadhanula, V., Piedra, P. A., Lichtarge, O., Shaw, C. A., Ronca, S. E., & Herman, C. (2024). Targeted accurate RNA consensus sequencing (tARC-seq) reveals mechanisms of replication error affecting SARS-CoV-2 divergence. Nature Microbiology, 9(5), 1382–1392. https://doi.org/10.1038/s41564-024-01655-4

Brogna, C., Cristoni, S., Marino, G., Montano, L., Viduto, V., Fabrowski, M., Lettieri, G., & Piscopo, M. (2023). Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms. PROTEOMICS – Clinical Applications, 17(6), 2300048. https://doi.org/10.1002/prca.202300048

Brogna, C., Viduto, V., Fabrowski, M., Cristoni, S., Marino, G., Montano, L., & Piscopo, M. (2023). The importance of the gut microbiome in the pathogenesis and transmission of SARS-CoV-2. Gut Microbes, 15(1), 2244718. https://doi.org/10.1080/19490976.2023.2244718

Chemaitelly H, Ayoub HH, Tang P, et al. Long-term COVID-19 booster effectiveness by infection history

and clinical vulnerability and immune imprinting: a retrospective population-based cohort study. The Lancet Infectious Diseases. 2023;23:816-27. https://doi.org/10.1016/S1473-3099(23)00058-0

Cobb, M. (2017). 60 years ago, Francis Crick changed the logic of biology. PLOS Biology, 15(9), e2003243. https://doi.org/10.1371/journal.pbio.2003243

Demongeot, J.; Fougère, C. mRNA COVID-19 Vaccines—Facts and Hypotheses on Fragmentation and Encapsulation. Vaccines 2023, 11, 40. https://doi.org/10.3390/ vaccines11010040

Diblasi, L., & Sangorrin, M. (Directors). (2024, April 3). Analysis on Covid-19 “vaccines” performed by Prof. Lorena Diblasi and Dr. Marcela Sangorrín [Video recording]. https://odysee.com/@laquintacolumnainternational:7/Analysis-on-Covid-19-vaccines-performed-by-Prof-Lorena-Diblasi-and-Dr-Marcela-Sangorrín:1

Fleming, D. R. M. (2021). Is COVID-19 a Bioweapon? A Scientific and Forensic Investigation. Skyhorse. https://www.simonandschuster.com/books/Is-COVID-19-a-Bioweapon/Richard-M-Fleming/Children-s-Health-Defense/9781510770195

Gutschi, M. (Director). (2022, November 2). Quality issues with mRNA Covid vaccine production [Video recording]. https://www.bitchute.com/video/muB0nrznCAC4/

Hamilton, R., Watanabe, C. K., & de Boer, H. A. (1987). Compilation and comparison of the sequence context around the AUG startcodons in Saccharomyces cerevisiae mRNAs. Nucleic Acids Research, 15(8), 3581–3593. https://doi.org/10.1093/nar/15.8.3581

Jeffrey, L. (2023, April 2). Funeral director Laura Jeffery on post-vaccine embalming. Canadian National Citizens Inquiry into COVID-19. https://www.youtube.com/watch?v=kYxUS9YO2rE

Lee, Y., & Broudy, D. (2024). Response to Critics of Lee & Broudy (2024) on the Toxicity and Self-Assembling Technology in Incubated Samples of Injectable mRNA Materials. International Journal of Vaccine Theory, Practice, and Research, 3(2), 1244.20-1244.29. https://doi.org/10.56098/aqgzye36

Lyons-Weiler, J. (2020). Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity. Journal of Translational Autoimmunity, 3, 100051. https://doi.org/10.1016/j.jtauto.2020.100051

Maass, H. (2020, December 11). 10 things you need to know today: December 11, 2020. Theweek. https://theweek.com/10things/954651/10-things-need-know-today-december-11-2020

McKernan, K., Kyriakopoulos, A., & McCullough, P. (2021). Differences in vaccine and SARS-CoV-2 replication derived mRNA: Implications for cell biology and future disease. https://doi.org/10.31219/osf.io/bcsa6

Mead, M. N., Seneff, S., Wolfinger, R., Rose, J., Denhaerynck, K., Kirsch, S., & McCullough, P. A. (2024a). COVID-19 modified mRNA “vaccines”, Part 1: Lessons learned from clinical trials, mass vaccination, and the bio-pharmaceutical complex. International Journal of Vaccine Theory, Practice, and Research, 3(1), 1112–1178. https://doi.org/10.56098/fdrasy50

Mead, M. N., Seneff, S., Wolfinger, R., Rose, J., Denhaerynck, K., Kirsch, S., & McCullough, P. A. (2024b). COVID-19 modified mRNA “vaccines”, Part 2: Lessons learned from clinical trials, mass vaccination, and the bio-pharmaceutical complex. International Journal of Vaccine Theory, Practice, and Research, 3(2), 1275-1344. https://doi.org/10.56098/w66wjg87

Mills, I., International Union of Pure and Applied Chemistry, & International Union of Pure and Applied Chemistry (Eds.). (1993). Quantities, units, and symbols in physical chemistry (2nd ed). Blackwell Scientific Publications ; CRC Press [distributor]. https://old.iupac.org/publications/books/gbook/green_book_2ed.pdf

Monroe, J. G., Mitchell, L., Deb, I., Roy, B., Frank, A. T., & Koutmou, K. (2022). N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation [Preprint]. Biochemistry. https://doi.org/10.1101/2022.06.13.495988

Mulroney, T. E., Pöyry, T., Yam-Puc, J. C., Rust, M., Harvey, R. F., Kalmar, L., Horner, E., Booth, L., Ferreira, A. P., Stoneley, M., Sawarkar, R., Mentzer, A. J., Lilley, K. S., Smales, C. M., von der Haar, T., Turtle, L., Dunachie, S., Klenerman, P., Thaventhiran, J. E. D., & Willis, A. E. (2023). N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. Nature, 625(7993), Article 7993. https://doi.org/10.1038/s41586-023-06800-3

Nance, K. D., & Meier, J. L. (2021). Modifications in an Emergency: The Role of N1-Methylpseudouridine in COVID-19 Vaccines. ACS Central Science, 7(5), 748–756. https://doi.org/10.1021/acscentsci.1c00197

National Center for Biotechnology Information. (2024a). PubChem Compound Summary for CID 6029, Uridine. [Dataset]. https://pubchem.ncbi.nlm.nih.gov/compound/Uridine

National Center for Biotechnology Information. (2024b). PubChem Compound Summary for CID 99543, 1-Methylpseudouridine [Dataset]. https://pubchem.ncbi.nlm.nih.gov/compound/1-Methylpseudouridine

National Library of Medicine. (2020). Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome (1798174254; Version 2) [Dataset]. NCBI Nucleotide Database. http://www.ncbi.nlm.nih.gov/nuccore/NC_045512.2

Nyström, S., & Hammarström, P. (2022). Amyloidogenesis of SARS-CoV-2 spike protein. Journal of the American Chemical Society, 144(20), 8945–8950. https://doi.org/10.1021/jacs.2c03925

Oller, J. W. (2022). Human Anatomy and Physiology: An Introduction for Undergraduate Students of Speech-Language Pathology and Audiology (3rd ed.). Sentia publishing. https://www.researchgate.net/publication/368752719_Human_Anatomy_Physiology

Oller, J. W., & Santiago, D. (2022). All cause mortality and COVID-19 injections: Evidence from 28 weeks of Public Health England “COVID-19 vaccine surveillance reports.” International Journal of Vaccine Theory, Practice, and Research, 2(2), 301–319. https://doi.org/10.56098/ijvtpr.v2i2.42

Pelech, S., & Shaw, C. A. (2024). Down the COVID-19 Rabbit Hole. Skyhorse Publishing. https://www.amazon.com/Down-COVID-19-Rabbit-Hole-Independent/dp/1510779590

Pharmaceutical Technology. (2024, July 5). COVID-19 Vaccination Tracker: Daily Rates, Statistics & Updates. Pharmaceutical Technology. https://www.pharmaceutical-technology.com/covid-19-vaccination-tracker/

Richter JD. Cytoplasmic polyadenylation in development and beyond. Microbiol Mol Biol Rev. 1999 Jun;63(2):446-56. doi: 10.1128/MMBR.63.2.446-456.1999. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC98972/

Ruggiero, R. P., & Boissinot, S. (2020). Variation in base composition underlies functional and evolutionary divergence in non-LTR retrotransposons. Mobile DNA, 11(1), 14. https://doi.org/10.1186/s13100-020-00209-9

Santiago, D. (2022a). A partial answer to the question posed by David A. Hughes, PhD, in the article: “What is in the so-called COVID-19 ‘vaccines’? Part 1: evidence of a global crime against humanity.” International Journal of Vaccine Theory, Practice, and Research, 2(2), 587–594. https://doi.org/10.56098/ijvtpr.v2i2.56

Santiago, D. (2022b). Playing Russian Roulette with every COVID-19 injection: The deadly global game. International Journal of Vaccine Theory, Practice, and Research, 2(2), 619–650. https://doi.org/10.56098/ijvtpr.v2i2.36

Santiago, D., & Oller, J. W. (2023). Abnormal clots and all-cause mortality during the pandemic experiment: Five doses of COVID-19 vaccine are evidently lethal to nearly all Medicare participants. International Journal of Vaccine Theory, Practice, and Research, 3(1), 847–890. https://doi.org/10.56098/ijvtpr.v3i1.73

Shrestha, N. K., Burke, P. C., Nowacki, A. S., Simon, J. F., Hagen, A., & Gordon, S. M. (2023). Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine. Open forum infectious diseases, 10(6), ofad209. https://doi.org/10.1093/ofid/ofad209

Speicher, D., Rose, J., Gutschi, L., Wiseman, D., & McKernan, K. (2023). DNA fragments detected in monovalent and bivalent Pfizer/BioNTech and Moderna modRNA COVID-19 vaccines from Ontario, Canada: Exploratory dose response relationship with serious adverse events. https://www.researchgate.net/publication/374870815_Speicher_DJ_et_al_DNA_fragments_detected_in_COVID-19_vaccines_in_Canada_DNA_fragments_detected_in_monovalent_and_bivalent/figures

Sun, S., & Fu, J. (2018). Methyl-containing pharmaceuticals: Methylation in drug design. Bioorganic & Medicinal Chemistry Letters, 28(20), 3283–3289. https://doi.org/10.1016/j.bmcl.2018.09.016

The Associated Press. (2022, December 14). Today in History: December 14, 2020 U.S. COVID vaccinations begin. AP News. https://apnews.com/today-in-history-december-14

Tuuminen, T. (2024). A GMO Experiment on Two-Thirds of the World’s Population: Reaction to Ulrich’s Commentary on Lee and Broudy (2024). International Journal of Vaccine Theory, Practice, and Research, 3(2), 1244.11-1244.18. https://doi.org/10.56098/xncqaa94

Ulrich, A. S. (2024). No Nanobots in Vaccines — Just Lipids on the Loose: Commentary on Lee and Broudy (2024), “Real-Time Self-Assembly of Stereomicroscopically Visible Artificial Constructs in Incubated Specimens of mRNA Products Mainly from Pfizer and Moderna: A Comprehensive Longitundinal Study.” International Journal of Vaccine Theory, Practice, and Research, 3(2), 1244.1-1244.10. https://doi.org/10.56098/7hsjff81

Walsh, D.J., Schinski, D.A., Schneider, R.A. et al. General route to design polymer

molecular weight distributions through flow chemistry. Nat Commun 11, 3094 (2020). https://doi.org/10.1038/s41467-020-16874-6

Veenstra, T. D., Pauley, B., Injeti, E., & Rotello, R. J. (2022). In vitro characterization of SARS-CoV-2 protein translated from the Moderna mRNA-1273 vaccine (p. 2022.03.01.22271618). medRxiv. https://doi.org/10.1101/2022.03.01.22271618

Vojdani, A., & Kharrazian, D. (2020). Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clinical Immunology (Orlando, Fla.), 217, 108480. https://doi.org/10.1016/j.clim.2020.108480

Vojdani, A., Vojdani, E., & Kharrazian, D. (2021). Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Frontiers in Immunology, 11, 617089. https://doi.org/10.3389/fimmu.2020.617089

Wayne, C. J., & Blakney, A. K. (2024). Self-amplifying RNA COVID-19 vaccine. Cell, 187(8), 1822-1822.e1. https://doi.org/10.1016/j.cell.2024.03.018

World Health Organization. (2020). Messenger RNA Encoding the Full-Length SARS-CoV-2 Spike Glycoprotein. International Nonproprietary Names, 11889.

Yıldız, A., Răileanu, C., & Beissert, T. (2024). Trans-amplifying RNA: A journey from alphavirus research to future vaccines. Viruses, 16(4), Article 4. https://doi.org/10.3390/v16040503

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Published

2024-10-10

How to Cite

A Closer Look at N1-methylpseudouridine in the Modified mRNA Injectables. (2024). International Journal of Vaccine Theory, Practice, and Research , 3(2), 1345-1366. https://doi.org/10.56098/5azda593

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