Multiple molecular checks ensure that the COVID-19 vaccine does not affect human DNA, thus, the chances of this occurring are highly improbable
A recent preprint (a study that has not yet been peer-reviewed) reports higher-than-expected levels of DNA in expired mRNA vaccine vials, but the results are preliminary and the suitability of the methods used to make this claim is debatable.The contaminating DNA Is presumably carried over from the process used to make the mRNA vaccines. For one thing, the mRNA vaccines have purification steps to remove this DNA (a circular plasmid from which the mRNA is synthesised). So, the amount of the contaminating DNA is likely to be low. A recent preprint (a study that has not yet been peer-reviewed) reports higher-than-expected levels of DNA in expired mRNA vaccine vials, but the results are preliminary and the suitability of the methods used to make this claim is debatable. However, the key point is that the presence of the contaminating DNA is only the first in a long chain of events. This DNA then has to get from the site of injection into cells, so the low amount of DNA is likely to get further diluted in the process. Thus, it is unlikely that there is enough of the contaminating DNA to get into many cells in large enough quantities. Next, the DNA has to cross the cell membrane, enter the cell/cytosol, and then go from the cytosol of the cell into the nucleus—a separate compartment for the DNA and closely associated proteins—this is like entering a fortress. To do this, there has to be enough DNA, which has not degraded in any way (double-stranded, and ends protected in some way—for instance, circular DNA of plasmids). Not surprisingly, a lot of the DNA is likely to be lost in transit. This, in fact, is a challenge that DNA vaccines need to overcome. This additional step (an extra membrane to cross cytosol-to-nucleus) is actually thought to be the reason that DNA vaccines produce a lower immune response as compared to mRNA vaccines. Once in the nucleus, this piece of DNA must be intact and have the features necessary to subvert the machinery of a cell, which must be a dividing cell (a non dividing cell would be an endpoint), and integrate into the DNA, bypassing all the checkpoints in place to prevent DNA damage… the same mechanisms that prevent tumours every time a cell makes a copy of itself. So, there are multiple molecular checks to ensure that such incorporation of DNA into the genome is rare. Having said that, some DNA viruses and viruses such as HIV are able to do it, so it is not entirely improbable. While integration can occur, it would be quite unlikely and one necessary step may be necessary for this piece of DNA to make copies of itself within the nucleus of a human cell, i.e., replication competence. Most of the COVID-19 vaccines are based on non-replicating vectors; this means that they do not have the sequences necessary to make copies of themselves even if they did get into a human cell.
While integration can occur, it would be quite unlikely and one necessary step may be necessary for this piece of DNA to make copies of itself within the nucleus of a human cell, i.e., replication competence.So, say at some really low frequency this integration/mutation does occur; this is not enough. It has to occur in regions that actually code for functional proteins to be properly disruptive. There are huge stretches of the genome that don’t code for anything; maybe it is meant to act as a buffer against foreign DNA onslaughts like this one, over thousands of years of evolution. Even if a piece of foreign DNA did make it all the way to the genome of a cell, this modification will likely die with the cell—most cells in the body are differentiated cells and have a short lifespan. To do real damage, such a DNA has to integrate within a gene of a stem cell, which lives in reasonably protected niches of the body. So, overall, the likelihood of contaminating DNA present in the vaccine impacting the human genome is astronomically low.
Additionally, in a healthy cell, the cellular defence against free-floating foreign RNA and DNA would likely kick in, thus making successful reverse transcription of mRNA vaccines very rare.This commentary has used the terms “unlikely” and “low probability” instead of “impossible” since organisms such as viruses have learnt how to break every rule in their host cell’s playbook to get ahead in the evolutionary race. This is why studies that look at different aspects of this process—starting from how much contaminating plasmid is present in the vaccine vial; is the load high enough to reach the cells; how many cells take up the DNA; does it get to the nucleus at all; does it persist there; does mRNA from the vaccine get converted to DNA within the body; when does it get cleared in different cell types, etc.—need to be done, rigorously and in multiple systems, especially as we gear up to use these vaccine technologies for more and more diseases. Presently, studies that raise alarms about the “integration” of COVID-19 vaccines and contaminating DNA, do not provide sufficient evidence across all these aspects to be taken seriously.
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