Orthogonal ensemble and single-particle characterisation of antisense oligonucleotide lipid nanoparticles

Abstract

Antisense oligonucleotide (ASO) lipid nanoparticles (LNPs) remain underexplored relative to siRNA and mRNA LNPs. Using an orthogonal workflow (DLS, NTA, AF4), we show that ionisable lipid identity and microfluidic flow rate govern key LNP attributes. Replacing SM-102 with MC3 increased size and reduced ASO recovery, while lower flow rates increased LNP size and improved recovery, highlighting formulation-property relationships for ASO LNP optimisation.

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