20α-Hydroxycholesterol is a naturally occurring oxysterol that plays a key role in regulating lipid metabolism and cellular signaling. It is an endogenous agonist of liver X receptors (LXRs), which are involved in controlling genes responsible for cholesterol transport and efflux. It also activates the Hedgehog pathway by binding the Smoothened receptor which then influences bone formation and developmental processes. Substituting sterols for cholesterol in lipid nanoparticle (LNP) formulations can influence morphology, internal structure, and endosomal escape. These analogs can result in substantial increases in gene delivery via LNPs.
