When it comes to mRNA-lipid nanoparticles (LNPs), the more mRNA they carry doesn’t always mean better delivery. A recent study, "Transfection Potency of Lipid Nanoparticles Containing mRNA Depends on Relative Loading Levels," led by Pieter R. Cullis and Anna K. Blakney from the University of British Columbia, Canada, reveals an intriguing paradox—LNPs with higher mRNA loading levels actually show lower transfection efficiency, both in vitro and in vivo.

Key Findings:

• Optimal Loading is Key: The study highlights that there is an optimal balance in mRNA loading; both overloading and underloading the mRNA cargo can reduce the effectiveness of the nanoparticles in delivering the mRNA into target cells.
• Transfection Potency vs. Payload: This challenges the long-standing assumption that maximizing mRNA payload always enhances the therapeutic potential of LNPs.

Why It Matters: These findings shift the focus from simply maximizing mRNA content to finding the sweet spot that optimizes transfection efficiency. This research opens new pathways for designing next-generation LNPs that ensure potent and efficient delivery, paving the way for more effective mRNA-based therapies.

Read more: https://pubs.acs.org/doi/10.1021/acsami.4c20077