Smarter Design for Better mRNA Delivery? It’s All About Tm 

Turns out, tuning the transition temperature (Tm) of helper lipids in LNPs can dramatically impact mRNA delivery efficiency. A recent study, "Transition temperature-guided design of lipid nanoparticles for effective mRNA delivery," by Jeong Kyu Bang, Michael J. Mitchell, Hyunjoo Cha-Molstad, and their teams from South Korea and the University of Pennsylvania (USA), reveals how optimizing lipid phase behavior boosts delivery performance both in vitro and in vivo.

Key Findings:
• Incorporating low-Tm helper lipids with high-Tm ionizable lipids lowers the overall Tm of the formulations, resulting in stable mRNA/LNPs with significantly improved transfection efficiency
• These formulations enhanced endosomal escape and mRNA release, leading to higher expression levels and improved mRNA delivery in both in vitro models and in vivo (mice)

Why It Matters:
This work underscores the importance of physicochemical fine-tuning in LNP design. By focusing on lipid Tm, researchers can engineer more effective delivery systems, accelerating the development of next-generation mRNA therapeutics and vaccines

Read more: https://doi.org/10.1021/acsami.5c06464