PUBMED Synthetic mRNAs; Their Analogue Caps and Contribution to Disease

This paper highlights an important concept of how mRNA is dramatically and potentially dangerously changing the balance of protein chemistry in the human body.  Now cited by PUBMED:
“The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins”

CONCLUSION
[…] The analogue caps of the synthetic mRNAs used for vaccination against cancer, genetic disorder therapy and nowadays as emerging for infectious diseases are optimized to stabilize and increase the translation of the encoded proteins in mRNAs and this is done to provide an efficient immunization. In this respect, attention should be made on studies that have shown that the enthalpic increase and entropic change between synthetic cap interactions with mammalian elF4E as well as with the elF4E of lower eukaryotic species may be in contrast to the elevation of complexity of living organisms in terms of growth rate requirements and compatibility with health (and life). However, our analysis reflects the potentiality to disease onsets by elF4E and mTOR deregulations. As the internal variables of a living organism are trying to keep its internal state unchangeable (homeostasis), and the reactions between analogue caps and elF4E are thermodynamically not favorable [1,2,3,4], this has to be analyzed by further superior physical chemistry, biochemistry and explicit toxicity evaluation research. Particularly during sensitive circumstances, as during deregulation of fine balance of cellular homeostasis (conditions of elF4E and mTORC1 deregulation) and as of this consequence, due to the autophagy deregulation, this is said to cause immune dysfunction irregularities, cellular maturation incompatibilities and predispose to various autoimmune disorders and malignancies. Foremost attention must be made to the potentiality of the loss of cap regulating innate defense of cells. By the alteration of regulation of cap methylation, this sets the organism susceptible to viral and bacterial infections as well as other diseases.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8395722/

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