> Over more than 3 decades, promising lipids studied in the lab often failed to live up to their potential when tested in animals or humans. Positively charged lipids are inherently toxic, and companies struggled for years before landing on formulations that were safe and effective. [0]
Lots of other details in this article of the problems they had over several decades finding lipids that worked and weren't toxic, wouldn't accumulate in the liver, etc.
The lipids used in the covid vaccines don't go back that far:
> The first time the FDA approved the use of lipid nanoparticles as a drug delivery system was in 2018, when the agency approved the first siRNA drug, Onpattro.[56] Encapsulating the mRNA molecule in lipid nanoparticles was a critical breakthrough for producing viable mRNA vaccines, solving a number of key technical barriers in delivering the mRNA molecule into the host cell. [1]
So they had something approved in 2018 for shorter siRNA payloads, but had to scramble since then to figure out something that would handle an mRNA payload.
[0] https://cen.acs.org/pharmaceuticals/drug-delivery/Without-li...
The right criterion: “Less dangerous than the disease itself”.
https://news.ycombinator.com/item?id=28108657
https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v...