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.