Why COVID-19 mRNA vaccines would not be reverse transcribed into DNA.

Some astute observers note that retroviruses use viral RNA and reverse-transcribe it into double stranded DNA and insert this DNA into the host genome. This is how retroviruses reproduce. The viral RNA in retroviruses is very similar to mRNA, since it has a cap and a poly-A tail and is made by cellular DNA-dependent RNA-polymerase. So, if a cell is infected with a retrovirus and a mRNA vaccine gets into that cell, maybe the mRNA from the vaccine could be reverse-transcribed into double stranded DNA and inserted into the cell’s genome, thereby changing the host DNA. There are also some endogenous retroviruses that are already in the genomes of all of our cells.

There are a number of reasons why this mRNA vaccine to DNA process would not happen. The first is that reverse transcription of viral RNA starts from a cellular transfer RNA (tRNA) primer that has to bind to the viral RNA. The mRNA vaccines do not have binding sites for a tRNA, so there would be nowhere for the reverse-transcriptase (the enzyme that copies the RNA into DNA) to start. The second is that all retroviruses have 2 copies of the viral RNAs that bind to each other through a special sequence called a kissing loop. Having two copies attached to each other through this kissing loop is essential for virus replication. The mRNA vaccines do not have this “kissing loop” sequence.

The third, and probably most important, reason is that reverse transcriptase stops when it tries to copy a RNA that contains a pseudo-uridine (a special modified base that is present in the tRNA primer that the reverse transcriptase used to start reverse transcription) instead of the normal uridine. This stopping is essential for the reverse transcriptase to make a double-stranded DNA that can be inserted into the genome (check out my Retrovirus lecture on YouTube for an explanation). The mRNA vaccines contain pseudouridine (actually 1-methyl pseudouridine) instead of the normal uridine to protect the vaccine from stimulating the immune system before it can do it’s job. So any reverse transcriptase that is trying to copy an mRNA vaccine into DNA, would stop before it had a chance to make double stranded DNA.

So, because the mRNA vaccines a) do not have a primer binding site, b) do not have a kissing loop structure, and c) contain pseudouridines instead of uridines they will not be copied into DNA by reverse transcription.