In vivo Characterization of T-Cell Activating Disulfide Lipids
Introduction
Lipid nanoparticles (LNP's) have emerged as promising vehicles to deliver a variety of therapeutics in vivo for the treatment and prevention of various diseases.
mRNA LNPs conventionally contain mRNA encapsulated in a lipid bilayer consisting of an ionizable lipid, a phospholipid, cholesterol, and a pegylated lipid.
The ionizable lipid generally contains an amino group, which electrostatically interacts with the phosphate groups on the mRNA backbone. The structure of the ionizable lipid impacts the efficacy, stability, and safety of mRNA LNP therapeutics. One of our successfully developed ionizable lipid families integrates a disulfide bond into the main structure. The reduction of disulfide bonds happens in endosomes that facilitate the endosomal escape of mRNA.