Figure 2.

Structure of LNP-Oligonucleotide Systems

(A) Molecular modeling¹⁷ indicates that LNP-nucleic acid systems contain irregular water-filled cavities surrounded by lipid monolayers, with nucleic acids bound to monolayer surfaces: cross-section and zoom views. Yellow, cationic lipid; pink, cholesterol; gray, DSPC; cyan, lipid polar moiety; violet, PEG-lipid; red, nucleic acids (duplex DNA); water not shown for clarity. The lipid composition was cationic lipid/DSPC/cholesterol/PEG-lipid (4:1:4:1; mol/mol) and DNA-to-lipid ratio ∼0.05 wt/wt. Adapted from Leung et al.¹⁷ (B) Lipid nanoparticle systems containing siRNA exhibit “solid core” morphology as visualized by cryo-TEM microscopy. Cryo-TEM micrograph obtained from LNP siRNA with lipid composition DLinKC2-DMA/DSPC/Chol/PEG-lipid (40/11.5/47.5/1; mol/mol) and siRNA at a siRNA/lipid ratio of 0.06, wt/wt, corresponding to an siRNA/cationic lipid charge ratio of 0.25. Scale bar, 100 nm. (C) LNP containing gold nanoparticles (5 nm diameter) exhibit a “currant bun” morphology.¹⁸ LNP encapsulating negatively charged gold nanoparticles (5 nm diameter) prepared with DLin-KC2-DMA/DOPE/Chol/PEG-lipid (40/11.5/47.5/1; % mol) at an Au-NP-to-lipid ratio of 2.2 × 10¹³ particles/μmol lipid. Scale bar, 100 nm.