Overcoming thermostability challenges in mRNA-lipid nanoparticle systems with piperidine-based ionizable lipids.

Lipid nanoparticles (LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed.

Effect of cationic lipid in cationic liposomes on siRNA delivery into the lung by intravenous injection of cationic lipoplex.

Cationic liposomes composed of dialkyl cationic lipid such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) can efficiently deliver siRNA to the lungs following the intravenous injection of cationic liposome/siRNA complexes (lipoplexes). In this study, we examined the effect of cationic lipid of cationic liposomes on siRNA delivery to the lungs after intravenous injection. We used six kinds of cationic cholesterol derivatives and 11 kinds of dialkyl or trialkyl cationic lipids as cationic lipids, and prepared 17 kinds of cationic liposomes composed of a cationic lipid and 1,2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) for evaluation of siRNA biodistribution and in vivo gene silencing effects.

Synthesis of Fused Carbazoles by Gold-Catalyzed Tricyclization of Conjugated Diynes via Rearrangement of an N-Propargyl Group.

Various N-propargylanilines bearing a conjugated diyne moiety at the 2-position were converted to tetracyclic fused carbazoles by treatment with a homogeneous gold(I) catalyst. This cascade reaction proceeds through indole formation with concomitant rearrangement of the N-propargyl group, intramolecular nucleophilic addition toward the resulting allene moiety, and subsequent hydroalkenylation. This transformation enables a one-pot synthesis of fused carbazoles from readily accessible substrates with 100% atom economy.