Notably and relevantly, it has been shown that inducing cells to favor cap-dependent translation via the high affinity between caps of synthetic mRNAs and eIF4E drives the recipient cells toward an increased tendency for proliferation and towards initiation of the cellular events that favor oncogenesis, immune dysregulation, and aging defects. The synthetic mRNA cap currently resident on the SARS-CoV-2 mRNA used for genetic vaccination is precisely the cap composition that favors cap-dependent translation of the mRNA. Furthermore, there are at least two additional cellular factors also driving cap-dependent translation in cells stressed by the presence of the synthetic mRNA and its spike protein product. These include a) the p38 MAPK pathway and, b) the imbalance of p53 inhibitory activity toward the mechanistic target of rapamycin (mToR) axis. [60].
In summary, the mRNA vaccines currently in use brings about a constellation of circumstances that drive cells toward cap-dependent translation of that mRNA – a process with a number of expected but not well characterized detrimental effects on cellular homeostasis.