Are mRNA vaccines gene therapy?
Some think the premise of this argument is that by using mRNA to elicit an immune response, it somehow means it’s not a vaccine.
mRNA is part of the system that translates the language of DNA (the blueprint) into proteins. DNA is the master copy in the nucleus, whereas mRNA is literally the messenger, taking copies out from the nucleus into the cytoplasm.
mRNA is made up of slightly different building blocks than DNA, so although it can move between the nucleus and cytoplasm, it chemically is impossible for it to be incorporated into DNA or alter it in any way.
Gene therapy involves using (amazing) new techniques to permanently alter defective sequences of DNA (genes) – requiring special enzymes and a targeted way of finding just one specific location of the defective gene. This is not yet approved for human use anywhere in the world, although some sneaky human uses have happened on 1-2 occasions.
A vaccine is anything that stimulates an immune response against a pathogen before we are exposed to the entire pathogen. The form of the vaccine can come in many different ways – attenuated, using another virus as a vector, proteins alone etc. mRNA vaccines have been in development for over 20 years, but the last time they got close to market, the SARS outbreak promptly was contained, and so they weren’t needed. The mRNA vaccines simply get our cells to make a protein rather than directly presenting a protein in the vaccine ingredients. They are super simple (just a lipid coat to protect them), and easily modifiable should the coding for the (spike) protein need to be changed – which could happen eg. Omicron.
So, in summary – mRNA cannot alter DNA, therefore it isn’t gene therapy, but it still IS a vaccine because it is training our immune system with a small part of the virus, to be prepared should we encounter the entire actual virus.
Is mRNA synthetic?
Firstly, although called a synthetic mRNA, N1-methylpseudouridine is actually a naturally occurring nucleotide in our cells – but it is normally found in tRNA (transfer), rather than mRNA (messenger). It is primarily used because it reduces the triggering of immune components associated with anaphylaxis, but can also boost the translation of the viral peptide (both things we want in a vaccine).
mRNA has a very short life span (minutes to days in mammalian cells), and gets degraded by enzymes in our cells called nucleases. Because the N1-methylpseudouridine is a natural nucleotide (albeit not normally in mRNA but rather tRNA), this also gets degraded. As uridines are pyramidine nucleotides, they are broken down fully into CO2 and NH3 (urea), and therefore able to be excreted fully.
Can the mRNA vaccine be incorporated into other human mRNA
Short answer is NO – N1-methylpseudouridine can’t be incorporated into other mRNA’s, because 1. The RNA polymerase enzyme that makes mRNA’s will not recognise it as a uridine, so exclude it from the process (which is happening in the nucleus), and 2. It would get broken down quickly and so excreted from the cytoplasm of the cell anyway.
