My wife works in biotech in Cambridge Mass, and the rumor is that Moderna is the next Theranos, and I heard this a couple years ago. So much so her PI recommended she not take a job there after grad school. Zero products and a thousand employees. This vaccine is also exceptionally good timing for their next equity raise, along with the CEO aggressively selling his stock.
My main concern is reading that there are no mRNA vaccines on the market but this would be the first. Really want to believe and hope in this vaccine but there are some red flags.
Massive red flags. No mRNA vaccine has made it to human trials, and all earlier attempts at vaccines for other coronaviruses (such as SARS/MERS) had some pretty bad side-effects such as immune enhancement.
Generating antibodies is one thing, but there have been SARS1 vaccines that generated antibodies and made the results worse:
Keep in mind we don't have vaccines for HIV or Herpes, but we do have effective drug treatment. It's much more likely we'll see a compound or procedure saving people from ARDS/Pneumonia than from a vaccine any time soon:
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.
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
5 comments
[ 419 ms ] story [ 1089 ms ] threadGenerating antibodies is one thing, but there have been SARS1 vaccines that generated antibodies and made the results worse:
https://www.pnas.org/content/117/15/8218
Keep in mind we don't have vaccines for HIV or Herpes, but we do have effective drug treatment. It's much more likely we'll see a compound or procedure saving people from ARDS/Pneumonia than from a vaccine any time soon:
https://battlepenguin.com/politics/this-is-not-a-time-of-hon...
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/