To summarize, Pfizer utilized lipid nanoparticles and a modified mRNA in which all natural uridine nucleotides were replaced with a rarely encountered nucleotide, N1-methylpseudouridine. While it solved their problems of RNA delivery, immunogenicity anddegradation, it created some new problems. While uridine substitution was found to reduce the body’s immune response to the foreign RNA and protect the mRNA from degradation, there are adverse effects from this strategy.
There is practically no scientific data available on how total uridine substitution in an mRNA will affect the delicate balance of the cellular and bodily physiology of the host and what downstream effects may be initiated. Yet Pfizer conducted no studies on this issue.
Suppressing the body’s innate immune system also has downstream consequences, particularly if a SARS-CoV-2 infection is subsequently encountered. Increasing the stability and half life of the vaccine mRNA, along with increasing its translation, means increased production of the spike protein which, as it turns out, is itself a cause of pathogensis.
Problems with the Pfizer vaccine design and failure to adequately investigate their effects on the delicate cellular systems of the human body are already manifesting themselves. These problems are summarized in VAERS (https://vaers.hhs.gov/about.html). The long list of adverse events is a reflection of these issues.
The use of messenger RNA (mRNA) vaccines has been developing since 1990. Historically, there have been three significant problems associated with mRNA vaccines. First, it has always been a challenge for vaccine developers to get the desired mRNA into the cells of choice (the delivery problem). Second, introducing a foreign RNA (the vaccine mRNA) into a patient causes their body to initiate an innate immune response thereby causing pathogenesis when there actually was no infection (the immunogenicity problem). And third, RNAs are rapidly degraded by ribonucleases (RNases) which are enzymes that degrade RNA. These RNases are found virtually everywhere which not only hinders development, but also makes it difficult to get a desired mRNA in a vaccine to stay around long enough to elicit the desired response (the degradation problem). There are many summaries of these historical facts (Morais et al., 2021; Jain et al., 2021; Kariko et al., 2008).
The claim among mRNA vaccine manufacturers and some scientists is that the three problems cited above have been solved; but have they?
Both Pfizer and Moderna claim that they solved these problems by encasing the mRNA inside of a lipid nanoparticle (LNP) and by modifying the mRNA through the substitution of N1-methylpseudouridine for the nucleotide uridine (Morais et al., 2021; Jain et al., 2021; Nance and Meir, 2021; Pardi et al., 2018; Andries et al., 2015). The use of LNPs allegedly solves the delivery problem by getting the vaccine’s modified mRNA into the cells and helping to protect the mRNA molecules from degradation during their trip from injection site to target cells. Their use of LNPs is another matter to be addressed in a subsequent report.
The use of a modified uridine (N1-methylpseudouridine) to replace uridine was suppose to solve the last two problems: the inherent immunogenicity of foreign mRNAs and degradation of the mRNA. These matters are the topic of this report.
Does the use of a modified uridine (N1-methylpseudouridine ) solve the problem of the immune response to a foreign RNA such as the vaccine delivered modified mRNA and premature degradation of the vaccine delivered mRNA?
It is difficult to dissect these two issues (mRNA immunogenicity and degradation) because they are so interconnected. But first, what is N1-methylpseudouridine and what does it do?