some stuff i'm reading re: vaccines
reading into dr. kariko's wiki page (won nobel prize last year for laying the groundwork for mrna as a vax platform w/ dr. weissman) and the fact that she got demoted at upenn beforehand and never received tenure is so insane to read: https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3
really interested in building in mrna vaccines and what problems i can work on to scale their reach globally. project lightspeed was like my version of a kid in the 60s watching the moon landing... i'm really excited about the progress we've made and the impact it holds for infectious diseases but specifically thinking about room for optimizing mrna vax biological properties for increased global viability. for the past while i've been curious about the problem of thermostability but i'm still working to map out (1) where we are with mrna vax thermostability, (2) what specifically needs to be optimized [or has highest leverage on overall stability] and (3) what's limiting our current methods of optimization. for ex. i've read a few papers about innovative drying methods (incl. lyophilization, supposedly less time and energy intensive than freeze drying) that remove all water from mrna vax formulations and dramatically reduce temperature sensitivity and increase shelf life by preventing degradation from mrna hydrolysis. what's stopping it from becoming commonplace? why's thermostability then still a problem we're trying to find solutions to? want to find answers to these questions + create a mental map of where we are and need to go
some stuff i recently found interesting:
ualbany's non-invasive innovation in testing for mrna vax integrity [but if it's designed to work for liquid formulations would it then be totally incongruent with lyophilized vax formulations? is this surmountable/circumventible?]
paper from may showing an increase in thermostability by engineering ionizable lipids in mrna-lnp formulations as piperidine-based lipids [synthetic lipids containing N-methyl piperidine head groups]. these lipids prevent production of fatty aldehyde impurities, here enabling the long-term storage of mRNAs/LNPs at 4 C (moderna, one of the more stable covid vax candidates, required -20C for 6 months)
this paper where the lyophilization procedure + choice of lyoprotectant is optimized, showing that it can make mrna-lnp vax formulations thermostable at temps similar to the paper above ^ while immunogenicity remained robust and lyophilized LNPs had no significant changes in particle size [which the paper above mentions as a concern for lyophilization]. lyophilization procedure here optimized to be much less time intensive ... papers like these without clear limitations outline make me wonder what's holding us back. is a decrease in lyophilization procedure duration 40-100h -> 8-18h still not attractive to big pharma companies? is cost the remaining factor to optimize? is it not an issue of incentivizing companies but something being fundamentally unfeasible/incongruent with current production pipelines? v curious and unaware
lots of stuff i read talks about the fundamental instability and unreliability of mrna as a biomolecule but it's interesting to see how that itself can also be optimized
protein vaccines, not mrna vaccines, but still found this pretty fascinating -- talk from the institute of protein design @ uw creating a platform to design antigen subunits that can self-assemble into large scaffolds (increases immunogenicity) with really beautiful mirroring to geometry and mathematical symmmetry
