Wednesday, January 31, 2024

The Terrifying & Frankensteinian Project to Bio-Engineer Your Proteins


Transfected mRNA in endothelial brain cells is Frankensteinian and raises very real risks for protein folding disorders given what we now know about "frameshifting" of protein production induced by the mRNA vaccines. (Note these are actually synthetic mRNA see my post here ).

Let us start by looking at the research article claiming to penetrate the blood-brain barrier using mRNA encased in lipid nanoparticles (LNPs):

Emily L. Han, Marshall S. Padilla, Rohan Palanki, Dongyoon Kim, Kaitlin Mrksich, Jacqueline J. Li, Sophia Tang, Il-Chul Yoon, and Michael J. Mitchell (2024). Predictive High-Throughput Platform for Dual Screening of mRNA Lipid Nanoparticle Blood–Brain Barrier Transfection and Crossing. Nano Lett. 2024, https://doi.org/10.1021/acs.nanolett.3c03509

Lipid nanoparticle (LNP)-mediated nucleic acid therapies, including mRNA protein replacement and gene editing therapies, hold great potential in treating neurological disorders including neurodegeneration, brain cancer, and stroke.
However, delivering LNPs across the blood–brain barrier (BBB) after systemic administration remains underexplored. In this work, we engineered a high-throughput screening transwell platform for the BBB (HTS-BBB), specifically optimized for screening mRNA LNPs.
Unlike most transwell assays, which only assess transport across an endothelial monolayer, HTS-BBB simultaneously measures LNP transport and mRNA transfection of the endothelial cells themselves.
We then use HTS-BBB to screen a library of 14 LNPs made with structurally diverse ionizable lipids and demonstrate it is predictive of in vivo performance by validating lead candidates for mRNA delivery to the mouse brain after intravenous injection. Going forward, this platform could be used to screen large libraries of brain-targeted LNPs for a range of protein replacement and gene editing applications.

  • Read Press Release here: https://penntoday.upenn.edu/news/bioengineers-brink-breaching-blood-brain-barrier
  • Also see publicity here:Tim Newcomb (2024, Jan 31). Scientists are about to break the blood-brain barrier- and maybe transform medicine. Popular Mechanics. https://www.popularmechanics.com/science/health/a46584155/blood-brain-barrier/

SO, what is being developed is a technique for bio-engineering how your brain cells produce proteins. NOW LET'S LOOK AT WHAT WE KNOW ABOUT FRAME-SHIFTING and explore the implications for how your body/brain produces proteins:

First, here is a press-release exploring frameshifting, or the glitching of protein production induced by the mRNA vaccines:

Pinkstone, Joe. (2023, December). Science Correspondent 6 December 2023 One in four who had Pfizer Covid jabs experienced unintended immune response https://www.telegraph.co.uk/news/2023/12/06/mrna-jabs-modena-pfizer-quarter-unintended-response/

mRNA vaccines were affected by the glitch but no adverse effects were created, Cambridge researchers say More than a quarter of people injected with mRNA Covid jabs suffered an unintended immune response created by a glitch in the way the vaccine was read by the body, a study has found. No adverse effects were created by the error, data show, but Cambridge scientists found such vaccines were not perfect and sometimes led to nonsense proteins being made instead of the desired Covid “spike”, which mimics infection and leads to antibody production. mRNA jabs, such as the ones created by Moderna and Pfizer, use a string of genetic material to tell the body to create a specific protein that safely imitates an infection. Research in the field, spanning decades, had been slow work. It often stalled because RNA itself is often attacked by the body as a foreign invader.

HERE IS THE RESEARCH STUDY upon which the press release is based:

Mulroney, T.E., Pöyry, T., Yam-Puc, J.C. et al. N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. Nature (2023). https://doi.org/10.1038/s41586-023-06800-

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2.

Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3,4,5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination.

The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products.

Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization.
BASICALLY, the process for engineering proteins is FULL OF ERRORS as the directions are subjected to frameshifting errors. So, mRNA produces MIS-FOLDED PROTEINS. 

I do not want misfolded proteins anywhere in my body, especially IN MY BRAIN.

IN OTHER NEWS - LEARN HOW SARS-CoV-2 viral proteins self-assemble into RNA that contribute to catastrophic auto-immune attacks:

SARS-CoV-2 viral fragments self-assemble into "new structures with double-stranded RNA, a special molecule essential for building proteins from DNA" and the resulting "hybrid complex of immune peptides and double-stranded RNA" produces a strong immune response.

California NanoSystems Institute JANUARY 29, 2024Viral protein fragments may unlock mystery behind serious COVID-19 outcomes https://medicalxpress.com/news/2024-01-viral-protein-fragments-mystery-covid.html

In a study appearing in the journal Proceedings of the National Academy of Sciences, a UCLA-led multidisciplinary research team explores one way that COVID-19 turns the immune system—which is crucial for keeping people alive—against the body itself, with potentially deadly results.

Using an artificial intelligence system they developed, the study authors scanned the entire collection of proteins produced by SARS-CoV-2 and then performed an exhaustive series of validation experiments. 

The scientists found that certain viral protein fragments, generated after the SARS-CoV-2 virus is broken down into pieces, can mimic a key component of the body's machinery for amplifying immune signals.

Their discoveries suggest that some of the most serious COVID-19 outcomes can result from these fragments overstimulating the immune system, thereby causing rampant inflammation in widely different contexts such as cytokine storms and lethal blood coagulation. 

…The research team found SARS-CoV-2 fragments can imitate innate immune peptides, a class of immune molecules that amplify signals to activate the body's natural defenses. Peptides are chains of amino acids like proteins, only shorter. 

These immune peptides can spontaneously assemble into new structures with double-stranded RNA, a special form of a molecule essential for building proteins from DNA, typically found in viral infections or released by dying cells.

The resultant hybrid complex of the immune peptides and double-stranded RNA kicks off a chain reaction that triggers an immune response. 

•More information: Yue Zhang et al, Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2300644120. doi.org/10.1073/pnas.2300644120

 The spike proteins produced by the mRNA vaccines will produce same effects!

RELATED POSTS

http://majiasblog.blogspot.com/2023/09/hazards-of-mrna-vaccine-platform.html


http://majiasblog.blogspot.com/2022/05/mrna-vaccines-linked-to-higher-cardio.html

http://majiasblog.blogspot.com/2022/04/fda-shuts-out-its-own-experts-in.html

http://majiasblog.blogspot.com/2022/03/thanatopolitics-and-vaccine-apartheid.html

http://majiasblog.blogspot.com/2021/08/what-is-going-on-no-public-health.html

http://majiasblog.blogspot.com/2021/06/spike-protein-blues.html

http://majiasblog.blogspot.com/2021/06/approval-mandatory-vaccine-mandates-for.html 

 

http://majiasblog.blogspot.com/2022/05/mrna-vaccines-linked-to-higher-cardio.html

http://majiasblog.blogspot.com/2022/04/fda-shuts-out-its-own-experts-in.html

http://majiasblog.blogspot.com/2022/03/thanatopolitics-and-vaccine-apartheid.html

http://majiasblog.blogspot.com/2021/08/what-is-going-on-no-public-health.html

http://majiasblog.blogspot.com/2021/06/spike-protein-blues.html

http://majiasblog.blogspot.com/2021/06/approval-mandatory-vaccine-mandates-for.html 









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