mRNA, synthetic mRNA (modified mRNA) formulated in lipid nanoparticles (LNPs) was always potentially TOXIC & all those involved knew it! 2017 study by Sedic is key in our understanding & why

by Paul Alexander

I call on Malone to explain what he knew & when about deleterious chromosomal changes reverse transcription, CDC lie it stayed at site, $ patents; we need answers; 2017 study raised risk questions!

SOURCE:

https://journals.sagepub.com/doi/10.1177/0300985817738095

 

Researchers studied synthetic mRNA and LNP activity via ‘repeat intravenous infusion to rats and monkeys. In both species, modified mRNA encoding the protein for human erythropoietin (hEPO) had predictable and consistent pharmacologic and toxicologic effects.

…The primary safety-related findings were caused by the exaggerated pharmacology of hEPO and included increased hematopoiesis in the liver, spleen, and bone marrow (rats) and minimal hemorrhage in the heart (monkeys).

…Additional primary safety-related findings in the rat included mildly increased white blood cell counts, changes in the coagulation parameters at all doses, as well as liver injury and release of interferon γ–inducible protein 10 in high-dose groups only.

…In the monkey, as seen with the parenteral administration of cationic LNPs, splenic necrosis and lymphocyte depletion were observed, accompanied with mild and reversible complement activation.’

‘From a safety perspective, modified mRNA delivered in LNPs is a complex molecule that requires the assessment of safety of the delivery system (LNPs), mRNA, and the translated protein product.’

Background:

‘Nucleotide-modified mRNA is nearly identical to naturally occurring mammalian mRNA, with the exception that certain nucleotides, normally present in mammalian mRNA, are partially or fully replaced with nucleosides, such as pyrimidine nucleosides—specifically, pseudouridine, 2-thiouridine, 5-methyl cytosine, or N1-methyl-pseudouridine.’

Pay attention to the term ‘systemic’:

‘Given the lability of a naked mRNA molecule, the development of mRNA therapeutics has been further hampered by the lack of appropriate formulations for delivery and potentially as a targeting mechanism to a diseased organ or tissue.12 However, the application of lipid-based nanoparticle delivery systems, initially developed for the in vivo delivery of siRNA, has enabled systemic administration of modified mRNA.22 Adequate delivery of mRNA with lipid nanoparticles (LNPs) has been demonstrated for mRNA-based vaccines, where intramuscular injection of low doses of mRNA formulated in either LNPs or nanoemulsion induced immune protection from influenza and respiratory syncytial virus in mice, as well as cytomegalovirus and respiratory syncytial virus in monkeys.9 Furthermore, a single administration of modified mRNA-LNP complexes in mice by various routes resulted in high, sustained protein production.19 Finally, Thess et al25 reported that repeated administration of unmodified mRNA in combination with the nonliposomal polymeric delivery system (TransIT) induced high systemic protein levels and strong physiologic responses in mice. These authors also noted similar observations following single-dose administration of erythropoietin (EPO)–mRNA in LNPs to pigs and monkeys.’

This type of paper needs relevant experts to dissect to help us understand fully but my reading of this 2017 paper tells me that many in this business knew of the challenges.