https://sciencebasedmedicine.org/rna...lter-your-dna/
This week, I wanted to cover something important that we haven?t covered before here at SBM. So I asked myself: What topic related to COVID-19 have we at SBM not covered yet that we really should have covered by now? Given that Steve has already covered the first two COVID-19 vaccines going to the FDA for approval and possible emergency use authorization (EUA), the Pfizer and Moderna vaccines, it didn?t make sense for me to discuss COVID-19 vaccines again. Then it occurred to me. These two new vaccines that will likely soon be available, at least to ?essential personnel? such as medical personnel treating COVID-19 patients anyway, share one thing in common. They are RNA vaccines. What also occurred to me is that there has been a persistent myth about RNA vaccines being promoted by the antivaccine movement. Perhaps you?ve seen it? Yes? No?
Perhaps you?ve seen memes like this:
False mRNA COVID vaccine meme
Or this one:
False COVID mRNA vaccine meme
Or this one:
False Bill Gates antivaccine meme
Or this one:
False COVID-19 mRNA vaccine meme
You get the idea. One major theme of antivaccine disinformation related to potential RNA vaccines against COVID-19 is that the RNA used in the vaccine will somehow permanently ?reprogram? your DNA in nefarious ways. It?s a claim that goes back at least to May, if not sooner, and arose as soon as antivaxxers became aware that one of the leading candidate vaccines against COVID-19 was Moderna?s RNA vaccine. After that, it soon became a standard talking point in the antivaccine movement?s pre-emptive disinformation war against COVID-19 vaccines. Why would anyone want to do this? Conspiracy theorists always have?reasons?of course. Some say that it?s to mark people. Some people say it?s to develop a technology that allows you to inject DNA directly into cells and reprogram them (Would that this were true! Such technologies would make gene therapy so much less difficult!) Often, antivaxxers conflate RNA with DNA and vice-versa, not realizing that, although both molecules contain genetic information needed for a cell to make protein, they are nonetheless very different in characteristics and behavior.
Of course, to experts the claim that RNA vaccines will somehow ?reprogram? your DNA claims are utterly risible in the ignorance of basic biology and biochemistry necessary to make such unscientific claims. But to nonexperts, most of whom probably long ago forgot their basic biology (if they ever learned it at all), the concept of a vaccine that turns your own cells into little factories making part of a key protein from COVID-19 that provokes a protective immune response (more on the specifics later) can seem quite plausible?and scary. Of course, fear is exactly the intended purpose of the antivaccine disinformation claiming that RNA vaccines will somehow ?reprogram? your DNA and permanently alter you genetically. (We do hope for one ?permanent? alteration in our biology as a result of a COVID-19, though, namely immunity to SARS-CoV-2, the coronavirus that causes COVID-19. Unfortunately, it?s not yet clear how long such immunity will last.) So let?s examine the claims being made and why you don?t have to fear RNA vaccines for COVID-19.
Before we do that, let?s look at what mRNA vaccines are, how they work, and what their advantages and disadvantages are compared to traditional vaccines.
mRNA vaccines
mRNA vaccines rely on something I?ve discussed before, namely the ?central dogma? of molecular biology. I must admit, I?ve always hated the use of the word ?dogma? associated with science, but no less a luminary than Francis Crick first stated it in 1958, and it has been restated over the years in various ways. Perhaps my favorite version of the central dogma was succinctly stated by Marshall Nirenberg in 1958 and has since been commonly paraphrased to say, ?DNA makes RNA makes protein?, which about summed up all of molecular biology in five words. (Why I used the past tense in a moment.) In any event, for purposes of understanding RNA viruses, this is the main sequence that you need to understand:
Central Dogma of Molecular Biology
Basically, DNA replicates from a DNA template and results in a double-stranded molecule that is very stable, as it has complementary sequences that tightly bind to each other in a sequence-specific fashion. This DNA template is unwound by enzymes that use the template to make RNA strands, which are single-stranded, which is then used by a ribosome to make protein out of amino acids. Again, to put it simply, each nucleotide equals one letter of the code; each three-nucleotide sequence (codon) equals one ?word? that translates to an amino acid. Given that there are four nucleotides, there are 64 possible codons. Since there are only 20 amino acids, that means that most amino acids are encoded by more than one combination of nucleotides or more than one codon; i.e., the genetic code is redundant. Of course, it?s more complicated than that, as this diagram shows:
Central Dogma Molecular Biology
Here?s a little video that?s useful too:
For instance, messenger RNA (mRNA) doesn?t always start out fully formed. Often it?s made as a longer precursor molecule that is spliced to the final mRNA sequence before being transported out of the nucleus into the cytoplasm to be used to make protein.
In fact, it?s even more complicated than that. Remember how I used the past tense when I said that the central dogma summed up all of molecular biology? It did, but then we started finding exceptions to the central dogma, such as retroviruses and microRNAs that can regulate gene expression, for instance. You don?t really need to know the gory details of many of these, although I will mention a couple of relevant ones and refer you to a post that does go into the gory details, for anyone who?s really interested.
Exceptions aside, RNA vaccines consist mainly of, well, RNA. One problem with RNA vaccines is that RNA is an inherently unstable molecule. It is, after all, a messenger. It doesn?t need to persist any longer than the message needs to be made. In aqueous solution, RNA molecules rapidly degrade. Indeed, the instability of RNA is why public health experts have been concerned about distributing RNA vaccines. Both companies adopted a similar strategy in designing their mRNA to encode the SARS-CoV-2 spike protein with stabilizing mutations added to lock this surface protein into a form easily recognizable to the immune system and therefore make it a better antigen. Pfizer and Moderna also used modified nucleosides (the RNA equivalent to DNA nucleotides) that are more stable to make their RNAs, and placed their RNA within a lipid nanoparticle (LNP) delivery system in which LNPs fuse with the cell membrane to deliver the RNA to the cytoplasm. Nonetheless, there are huge differences in the temperatures at which these vaccines need to be stored to remain stable and active.
Here?s what I mean. The Pfizer vaccine (developed in partnership with a company called BioNTech) reportedly needs to be stored at -80?C. While I have a -80?C freezer in my laboratory (to store RNA samples, among other things), most physicians? offices and clinics do not, because such freezers are large and very expensive compared to the more common refrigerators (which generally maintain a temperature of around 4?C) and standard freezers (which maintain a temperature of around -20?C). Even many hospitals do not have enough -80?C freezers to store large quantities of vaccine. Similarly, because of the temperature necessary to keep the vaccine stable and active, transporting the Pfizer vaccine presents logistical challenges, because the vaccine must be kept at -80?C or colder during the entire chain of transport. It can be done, using dry ice, of course, but it?s difficult, and one could easily imagine an impending dry ice shortage once such vaccines roll out. To this end, both companies have apparently used modified nucleotides to try to make their mRNA molecules more stable The Moderna vaccine, in contrast, can reportedly be stored at -20?C for up to six months, which is much more doable, as most standard freezers can reach this temperature. Even better, the Moderna vaccine will remain stable at standard refrigerator temperatures of 2? to 8?C (36? to 46?F) for up to 30 days and remains stable at room temperature for up to 12 hours. Why the difference? It?s hard to know for sure, as both companies are tight-lipped about the exact differences in their vaccines. A Moderna spokesperson explained to NPR: