Disorder Wins: a Breakthrough in mRNA Delivery

Copenhagen scientists find disordered LNPs release mRNA more effectively, reshaping drug delivery design

13 May 2026

For decades, the assumption was simple: pack mRNA delivery vehicles as tightly as possible. Neat structure meant reliable medicine. Scientists at the University of Copenhagen just turned that logic on its head.

Their research, presented at the 70th Biophysical Society Annual Meeting in February 2026, found that lipid nanoparticles (LNPs) with disordered, "messier" internal structures release their mRNA cargo far more effectively than their neatly organized counterparts. It's a finding that could reshape cancer treatment, gene therapy, and vaccine design.

The breakthrough required a new way of looking. The team built a measurement platform capable of analyzing one million individual nanoparticles simultaneously, rather than relying on batch averages that mask what's actually happening particle by particle. What they found was striking: standard LNP samples contain two distinct structural populations. One is tightly organized. The other is loose, amorphous, almost chaotic-looking. The messy ones perform better.

Charge separation appears to be why. Rigid, well-organized particles resist releasing their payload once inside a cell. Looser structures respond more fluidly to the cell's electrochemical environment, giving up their contents when and where it counts. Right now, only 1 to 5 percent of LNP cargo reaches its target, a shortfall that significantly limits what mRNA therapies can achieve, particularly in oncology, where tumors are fast-moving targets.

Lead researcher Artu Breuer is clear that the goal isn't to load less RNA into each particle. It's to find formulations that preserve structural looseness without sacrificing carrying capacity. Translating that into pharmaceutical-grade manufacturing will take more work, and open questions remain about how findings hold across different RNA sequences, targets, and delivery methods.

Still, the platform itself may matter as much as the discovery. Giving scientists particle-level visibility into nanoparticle behavior is a step toward building RNA medicines that don't just carry their cargo, but reliably deliver it.