[jasonmar]

It would be fantastic if Moderna can manufacture and deliver the mRNA into human cells cost effectively and at scale.

Outside the cell, there are enzymes that cut up mRNA. So lipid nanoparticles are used to protect the mRNA. But then even if this makes it into the cell, the nanoparticle itself can be ejected by cell machinery.

If the mRNA can avoid ribonuclease long enough for the mRNA to be translated into protein rather than being degraded, then it seems pretty straightforward that the protein may be bound by MHC and make it to antigen presentation, T cell activation, B cell activation and hopefully affinity maturation and Memory B cells for the viral protein.

This paper explains some of the challenges: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453548/

[jryb]

i’m super foggy on the details, but in a talk a few months before the shutdown the CSO from moderna said they add some sort of functional group to inhibit degradation. i believe it was more complicated than just “ligate something that endonucleases can’t bind” and there were interesting reasons why, but i bet this information is available somewhere since the slides were made for investors. again my memory is super unreliable but i was definitely wondering how they got around that before she addressed it