Calculating\nApparent p<i>K</i><sub>a</sub> Values of Ionizable Lipids\nin Lipid Nanoparticles

Creating new ionizable lipids for use in lipid nanoparticles\n(LNPs)\nis an active field of research. One of the critical properties for\nselecting suitable ionizable lipids is the apparent p<i>K</i><sub>a</sub> value of the lipid as formulated in an LNP. We have\ndeveloped a structure-based, computational methodology for the prediction\nof the apparent p<i>K</i><sub>a</sub> value of ionizable\nlipids within LNPs and have tested it using the lipid formulations\nin the mRNA LNP COVID-19 vaccines COMIRNATY and Spikevax, and the\nsiRNA LNP therapeutic Onpattro. The calculation was also applied to\nLipid A, a variant of the ionizable lipid used in COMIRNATY.