Category Archives: immunology

a brief look at mRNA biotech

from ScienceDirect: The mechanisms of different nucleic acid vaccines, including DNA vaccines, mRNA vaccines.

So it’s been three years since I’ve written on this blog, and I feel it’s time to revive it, and explore human optimism, innovation and all that positive stuff. I plan to revisit some of the innovations and pathways I’ve looked at before, to update my knowledge and check on progress, as well as checking out new developments to expand my range and keep my brain from atrophying.

So I’ll start with vaccination. The ongoing pandemic, that we here in Australia have largely dodged, has brought about an unprecedented response from virologists, completely upending the standard lag time between identifying the pathogen and having a vaccine, in fact more than one, produced in such numbers as to induce herd immunity and bring the situation more or less under control.

Not long after SARS-CoV2 was identified, drug and biotech companies began a billion-dollars race to create a big name for themselves. Two of them, Pfizer, in collaboration with German biotech company BioNTech, and Moderna, have gained the most publicity, not only for being front-runners, but for having based their vaccine on messenger RNA (mRNA).

A November 10 article from STAT+ and the Boston Globe has helped me understand the significance. The idea, once the genetic sequence of the virus is known, is to create a synthetic variant of mRNA which could then make proteins (antibodies) which would inactivate the virus.

This is the role of mRNA in all our cells. It’s translated into proteins by means of our ribosomes, and these proteins are then dispatched to perform an endless variety of roles throughout our body, including as antibodies to prevent infections, and enzymes to repair tissues. The potential of synthesising mRNA for specific purposes – to fight disease and build immunity, for example – was recognised decades ago, but every attempt to inject synthetic mRNA met with failure, as the body’s immune system recognised a chemical intruder and mounted a vigorous response. However, this problem was eventually overcome, at least partially (this is still experimental and developing technology), by swapping out one of the four nucleosides that make up every strand of mRNA for a modified version. The hybrid mRNA is able to act within cells without invoking a killing immune response. The referenced article tells the story of how this development took some years to be recognised within the biotech community, in spite of a number of published papers. It’s a human story of egos and squabbles over priority, unsurprisingly, but I just want to focus on current implications. When the technology became known in the USA, it was first mooted as a way to reprogram somatic cells into embryonic stem cells. But soon, researchers noted the vast possibilities of a technology that could induce protein production in the body for a whole host of purposes – perhaps only limited by the innumerable roles proteins naturally perform in the body.

The technology, however, still faces many hurdles, mostly related to immune responses. In recent times it has limited its focus to vaccines, and this meant that it was ideally placed to tackle the current covid-19 pandemic. Clearly we have to wait awhile for a final verdict on the two mRNA vaccines now being produced and administered around the world, but, generally, so far, so good. I’m sure there will be more to write about re synthesised mRNA technology in the future.

References

The article below, mentioned in my piece, provides a more comprehensive, and fascinating, behind-the-scenes view of some of the people involved in this technology.