Cubic Phase‐Inducible Zwitterionic Phospholipids Improve the Functional Delivery of mRNA (Adv. Sci. 17/2025)

Zwitterionic Phospholipids In article number 2413016, Yusuke Sato and co‐workers develop engineered zwitterionic phospholipid, DOPE‐Cx, originated from naturally occurring fusogenic phospholipid. Structure‐activity relationship study reveals that DOPE‐Cx derivatives inducing cubic phase upon mixing with endosomal membrane‐constituting phosphatidylcholines significantly improve membrane disrupting activity of lipid nanoparticles in weakly acidic pH and promote cytosolic delivery of exogenous mRNAs. [Image: see text]