Figure 7.

Cellular efficacy of ASO-LNPs is governed by the extent of order within their core. The various structural features are shown in four different colors. The dots represent the ASO-lipid compartmentalization, and the circles represent the ASO-lipid bilayers. The medium-size LNPs with a hydrodynamic diameter (D_h) of 100–155 nm and low nonorder-to-order ratios (disordered/H_II) show the best in vitro efficacy. Small LNPs (D_h < 100 nm) feature abundant disordered phases but lack the ordered structure in the particle core, whereas very large LNPs (D_h > 155 nm) show unstable crystalline structure with reduced hexagonal phase in the particle core. Both scenarios lead to high disordered/H_II ratios, correlating with diminished in vitro efficacy.