Page 6 - Dr Stephanie Seneff - Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID - 19

needed for immunogenesis (Liu, 2019). This form of mRNA delivered in the vaccine is never seen in
nature, and therefore has the potential for unknown consequences.

The Pfizer-BioNTech and Moderna mRNA vaccines are based on very similar technologies, where a
lipid nanoparticle encloses an RNA sequence coding for the full-length SARS-CoV-2 spike protein.
In the manufacturing process, the first step is to assemble a DNA molecule encoding the spike
protein. This process has now been commoditized, so it’s relatively straightforward to obtain a
DNA molecule from a specification of the sequence of nucleotides (Corbett et al., 2020). Following
a cell-free in vitro transcription from DNA, utilizing an enzymatic reaction catalyzed by RNA
polymerase, the single-stranded RNA is stabilized through specific nucleoside modifications, and
highly purified.

The company Moderna, in Cambridge, MA, is one of the developers of deployed mRNA vaccines
for SARS-CoV-2. Moderna executives have a grand vision of extending the technology for many
applications where the body can be directed to produce therapeutic proteins not just for antibody
production but also to treat genetic diseases and cancer, among others. They are developing a
generic platform where DNA is the storage element, messenger RNA is the “software” and the
proteins that the RNA codes for represent diverse application domains. The vision is grandiose and
the theoretical potential applications are vast (Moderna, 2020). The technology is impressive, but
manipulation of the code of life could lead to completely unanticipated negative effects, potentially
long term or even permanent.

SARS-CoV-2 is a member of the class of positive-strand RNA viruses, which means that they code
directly for the proteins that the RNA encodes, rather than requiring a copy to an antisense strand
prior to translation into protein. The virus consists primarily of the single-strand RNA molecule
packaged up inside a protein coat, consisting of the virus’s structural proteins, most notably the
spike protein, which facilitates both viral binding to a receptor (in the case of SARS-CoV-2 this is
the ACE2 receptor) and virus fusion with the host cell membrane. The SARS-CoV-2 spike protein is
the primary target for neutralizing antibodies. It is a class I fusion glycoprotein, and it is analogous to
haemagglutinin produced by influenza viruses and the fusion glycoprotein produced by syncytial
viruses, as well as gp160 produced by human immunodeficiency virus (HIV) (Corbett et al., 2020).

The mRNA vaccines are the culmination of years of research in exploring the possibility of using
RNA encapsulated in a lipid particle as a messenger. The host cell’s existing biological machinery is
co-opted to facilitate the natural production of protein from the mRNA. The field has blossomed in
part because of the ease with which specific oligonucleotide DNA sequences can be synthesized in
the laboratory without the direct involvement of living organisms. This technology has become
commoditized and can be done at large-scale, with relatively low cost. Enzymatic conversion of
DNA to RNA is also straightforward, and it is feasible to isolate essentially pure single-strand RNA
from the reaction soup (Kosuri and Church, 2014).

1. Considerations in mRNA Selection and Modification
While the process is simple in principle, the manufacturers of mRNA vaccines do face some
considerable technical challenges. The first, as we’ve discussed, is that extracellular mRNA itself can
induce an immune response which would result in its rapid clearance before it is even taken up by

International Journal of Vaccine Theory, Practice, and Research 2(1), May 10, 2021 Page | 394