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mRNA COVID-19 Vaccines-Facts and Hypotheses on Fragmentation and Encapsulation

Jacques Demongeot1, Cécile Fougère1

  • 1AGEIS & Telecom4Health, Faculty of Medicine, University Grenoble Alpes, 38700 La Tronche, France.

Vaccines
|January 21, 2023
PubMed
Abstract

Insights

Messenger RNA (mRNA) vaccines, initially developed for influenza, have been adapted for SARS-CoV-2. Research suggests potential mRNA fragmentation and biodistribution issues with lipid nanoparticles (LNPs), necessitating personalized vaccine strategies.

Area of Science:

  • Vaccinology
  • Molecular Biology
  • Virology

Background:

  • Messenger RNA (mRNA) vaccine technology originated from influenza research approximately 30 years ago.
  • Early mRNA vaccines involved encapsulating mRNA encoding viral proteins within lipid particles.
  • Current mRNA vaccines for SARS-CoV-2 utilize modified mRNA encoding the S protein.

Purpose of the Study:

  • To investigate the modifications of mRNA encoding the S protein for anti-SARS-CoV-2 vaccination.
  • To assess the theoretical possibility of mRNA fragmentation and its potential impact on cellular biosynthesis.
  • To analyze the role of liposomal nanoparticles (LNPs) in mRNA vaccine biodistribution and potential adverse effects.

Main Methods:

  • Analysis of genetic and epidemiologic databases.
  • Theoretical modeling of mRNA fragmentation and its biological consequences.
  • Evaluation of LNP characteristics and their influence on mRNA biodistribution.

Main Results:

  • Demonstrated the theoretical possibility of mRNA fragmentation into small RNA sequences.
  • Identified potential inhibition of essential biosynthetic pathways, such as beta-globin production, due to fragmented mRNA.
  • Highlighted concerns regarding mRNA biodistribution influenced by LNPs.

Conclusions:

  • Discussed the plausibility of mRNA fragmentation in vaccines.
  • Emphasized the need for improved LNPs for personalized vaccine administration to mitigate adverse effects.
  • Recommended adapting vaccine mRNA to less mutated viral proteins and tailoring administration for at-risk patient groups.
Keywords:
SARS-CoV-2circular RNAliposomemRNAmicroRNAvaccine

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