No, Really, mRNA Vaccines Are Not Going To Affect Your DNA

The short version: There is no plausible way that mRNA vaccines are going to alter your DNA. It would violate basically everything we know about cell biology.

Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K. Molecular cell biology. 8th ed. New York: W.H. Freeman; 2016. Figure 5–1 This figure is useful because you can clearly see the two compartments we care about: the nucleus, which houses almost all of the DNA (exception discussed), and the cytosol, which is where translation happens.
Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K. Molecular cell biology. 8th ed. New York: W.H. Freeman; 2016. Figure 13–37B which demonstrates the export of mRNA from the nucleus.
Flint S, Racaniello V, Rall G, Skalka A, Enquist L. Principles of virology. Washington, DC: ASM Press; 2015. Figure 5.23C which shows the nuclear import cycle with influenza ribonucleoproteins as an example. Nucleear localization signals are recognized by importin-α which then recruits importin-β which recruits a small GTPase called Ran. When binding GDP, Ran is able to transport the RNP across the nuclear pore complex. The complex of importins and Ran will then dissociate, and a guanine nucleotide exchange factor will exchange GDP for GTP, that allows Ran-GTP to be exported out of the nucleus. RanGAP-1 or RanBPI, 2 can then catalyze hydrolysis of GTP to GDP which allows Ran to bind another importin-β to initiate the import cycle once more.
  • Hepadnaviruses are DNA viruses which have gapped genomes (there is one complete DNA strand and another partial DNA strand which is linked to a pregenomic RNA), and unlike retroviruses, do not integrate into the genome of the host cell they infect. The most famous example is Hepatitis B virus, for which multiple effective vaccines exist.
  • Telomeres are structures present at the ends of human chromosomes which are maintained by a protein complex called telomerase that uses a reverse transcriptase called TERT to maintain them. The reasons this is necessary are discussed in Figure 9–12 on the left. They are about 5–15 kilobases long normally, and shortening results in arrest of cell growth and replication (senescence), or can even trigger cell death by apoptosis.
  • Retrotransposons are actually the most abundant component of our genome. The human genome contains about 21,000–27,000 genes (the number you get depends on how precisely you define a gene and which source you consult), which span 40–48 million base pairs, but this accounts for only about 1.5% of the 3.2 billion total base pairs. Retrotransposons account for about 2 billion base pairs. There are several kinds of retroelements, which are worth discussing further:
Hartwell L, Goldberg M, Fischer J, Hood L. Genetics. 6th ed. New York: McGraw Hill; 2018. Table 13–2
  1. LINEs (long interspersed nuclear elements) which encode a reverse transcriptase formed from the ORF1 and pol genes which can copy itself and other LINE and SINE elements into other regions of the genome.
  2. About 5–8% of the human genome is also composed of human endogenous retroviruses, HERVs, which also fall into the category of retrotransposons, more specifically LTR (long terminal repeats) retrotransposons (more on this shortly). HERVs contain 3 genes: gag (“group antigens,” which encodes a polyprotein that is cleaved into the structural proteins of the resultant retrovirus), pol (the reverse transcriptase needed for the virus to replicate), and env (envelope, which encodes the protein that gives the viral particles their shape).
  3. More broadly, the term retroelement refers to genetic sequences that have moved from one region of the genome to another via reverse transcription, and these include retrotransposons, and processed pseudogenes. Processed pseudogenes refer to the sequences of processed mRNA that lack introns that have been inserted via reverse transcription (we know they had to be inserted into the genome via reverse transcription in large part because they lack introns). They are incapable of producing any gene product.
  4. The only retrotransposons that can move through the genome (literally copy their DNA to new sites where it was not initially present) are the LINEs and SINEs, and of these, only a few are able to accomplish this. HERVs are stuck where they are, and processed pseudogenes are as well.
Linares-Fernández S, Lacroix C, Exposito J-Y, Verrier B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends in molecular medicine. 2020;26(3):311–323. Figure 2 The basic organization of an mRNA vaccine’s sequence
Zhang Q, Kim N-K, Feigon J. Architecture of human telomerase RNA. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(51):20325–20332. Figure 1
Hartwell L, Goldberg M, Fischer J, Hood L. Genetics. 6th ed. New York: McGraw Hill; 2018. Figure 12.20 showing the mechanism by which telomerase produces the telomere. the RNA primer
Flint S, Racaniello V, Rall G, Skalka A, Enquist L. Principles of virology. Washington, DC: ASM Press; 2015. Figure 7.2

There is no feasible means by which an mRNA vaccine could end up in the nucleus of a cell, nor prime a reverse transcription reaction, nor give you a mitochondrial disease.

There is no reasonable possibility based on the totality of our knowledge of cell biology, reverse transcriptases, human genetics, and the immune system that mRNA vaccines can affect your DNA.

We should await the detailed safety data, but, a priori, a segment of RNA encoding the spike protein RBD or even the whole spike protein of SARS-CoV-2 with no replicative potential, and no ability to form whole virus, nor even whole ability to form an ENTIRE spike protein, should be expected to be a safe vaccine that isn’t going to cause these insane pie-in-the-sky science fiction scenarios.

If you are worried about the mRNA vaccines, then don’t get them. The data suggest that there will soon be other kinds of vaccines with good efficacy as well. I, however, am content to roll up my sleeves for one of them.

The inimitable Professor Vincent Racaniello created this spectacular animation which demonstrates precisely how retroviruses like HIV replicate, for those who may be interested.

References

  1. Hartwell L, Goldberg M, Fischer J, Hood L. Genetics. 6th ed. New York: McGraw Hill; 2018.
  2. Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K. Molecular cell biology. 8th ed. New York: W.H. Freeman; 2016
  3. Flint S, Racaniello V, Rall G, Skalka A, Enquist L. Principles of virology. Washington, DC: ASM Press; 2015.
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I write about vaccines here. You can find me on Twitter @enirenberg and at deplatformdisease.com (where I publish the same content without a paywall)

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