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mRNA Vaccines: Why Is the Biology of Retroposition Ignored?

Domazet-Lošo, Tomislav (2022) mRNA Vaccines: Why Is the Biology of Retroposition Ignored?. Genes, 13 (5). ISSN 2073-4425

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The major advantage of mRNA vaccines over more conventional approaches is their potential for rapid development and large-scale deployment in pandemic situations. In the current COVID-19 crisis, two mRNA COVID-19 vaccines have been conditionally approved and broadly applied, while others are still in clinical trials. However, there is no previous experience with the use of mRNA vaccines on a large scale in the general population. This warrants a careful evaluation of mRNA vaccine safety properties by considering all available knowledge about mRNA molecular biology and evolution. Here, I discuss the pervasive claim that mRNA-based vaccines cannot alter genomes. Surprisingly, this notion is widely stated in the mRNA vaccine literature but never supported by referencing any primary scientific papers that would specifically address this question. This discrepancy becomes even more puzzling if one considers previous work on the molecular and evolutionary aspects of retroposition in murine and human populations that clearly documents the frequent integration of mRNA molecules into genomes, including clinical contexts. By performing basic comparisons, I show that the sequence features of mRNA vaccines meet all known requirements for retroposition using L1 elements—the most abundant autonomously active retrotransposons in the human genome. In fact, many factors associated with mRNA vaccines increase the possibility of their L1- mediated retroposition. I conclude that is unfounded to a priori assume that mRNA-based therapeutics do not impact genomes and that the route to genome integration of vaccine mRNAs via endogenous L1 retroelements is easily conceivable. This implies that we urgently need experimental studies that would rigorously test for the potential retroposition of vaccine mRNAs. At present, the insertional mutagenesis safety of mRNA-based vaccines should be considered unresolved.

Item Type: Article
Uncontrolled Keywords: mRNA vaccines ; retroposition ; L1 elements ; LINE-1 ; retrotransposons ; retrocopy ; parental genes ; genome integration ; insertional mutagenesis
Subjects: NATURAL SCIENCES > Biology
Divisions: Division of Molecular Biology
Project titleProject leaderProject codeProject type
Filostratigrafija nastanka i gubitka genaDomazet-Lošo, TomislavIP-2016-06-5924HRZZ
Napredne metode i tehnologije u znanosti o podatcima i kooperativnim sustavimaUNSPECIFIEDUNSPECIFIEDEK
Depositing User: Tomislav Domazet-Lošo
Date Deposited: 28 Jun 2022 13:26
DOI: 10.3390/genes13050719

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