siRNA/mRNA payload of lipid nanoparticles quantified using fluorescence microscopy and correlation spectroscopy

FCS quantifies mRNA payload in lipid nanoparticles reliably across fluorophore changes, and mRNA payload for eGFP coding mRNA scales with LNP size by a power law exponent of 1.3.

• Why it matters: Reliable RNA payload and LNP size measurements are needed to evaluate advanced delivery strategies that co-deliver multiple nucleic acid species.
• What they did: Using TIRF microscopy and fluorescence correlation spectroscopy, the study measured mRNA payload and siRNA/mRNA codelivered payload while varying PEG-lipid fraction versus the ONPATTRO reference formulation.
• The result: mRNA payload increases from [~]10 with LNP size following the exponent 1.3, Cryo-EM shows more frequent blebs in smaller LNPs, and siRNA fraction inside LNPs exceeds that in the initial RNA mixture.

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