Calculating Apparent p<i>K</i>_a Values of Ionizable Lipids in Lipid Nanoparticles.

ABSTRACT: Creating new ionizable lipids for use in lipid nanoparticles (LNPs) is an active field of research. One of the critical properties for selecting suitable ionizable lipids is the apparent pK_a value of the lipid as formulated in an LNP. We have developed a structure-based, computational methodology for the prediction of the apparent pK_a value of ionizable lipids within LNPs and have tested it using the lipid formulations in the mRNA LNP COVID-19 vaccines COMIRNATY and Spikevax, and the siRNA LNP therapeutic Onpattro. The calculation was also applied to Lipid A, a variant of the ionizable lipid used in COMIRNATY.

SUBMITTER: Hamilton NB 

PROVIDER: S-EPMC11707724 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature