Fig. 5: aNP formulations for ASO and messenger RNA delivery to immune cells.
a, aNP-ASO composition (wt%). b, Cryo-EM image. c, Schematic of NATURA reporter cells that alter the expression of eGFP to tRFP upon ASO-mediated splice-switching37. d, Splice-switching in RAW 264.7 reporter cells in vitro. Data represent mean ± s.d. of two experiments with two formulation batches (n = 2). e, aNP-mRNA composition (wt%). f, Cryo-EM image. g, Hydrodynamic diameter represented as the number mean and dispersity. Data represent mean ± s.d. of one experiment with 14 formulation batches (n = 14). h, mRNA recovery, entrapment and retention data represent mean ± s.d. of one experiment (n = 14 formulation batches). i, Zeta potential data represent mean ± s.d. of one experiment with three individual formulations (n = 3 formulations). j,k, Schematic workflow of intravenously (i.v.) administering aNPs containing mCherry mRNA (aNP-mRNA-mCherry) (j) at a dose of 0.5 mg kg–1 mRNA to C57/BL6 mice and determining expression in bone marrow cells by flow cytometry analysis (k). l, mCherry expression in bone marrow myeloid progenitors indicated by geometric mean fluorescence intensity (gMFI, left panel) and percentage of mCherry+ cells (right panel) 12 h after intravenous administration with LNP and aNP containing mCherry mRNA. Data represent mean ± s.d. of one experiment (n = 3 mice) and analysed by student t-test. Statistically significant differences between LNP-mRNA versus aNP-mRNA formulations are indicated by: *P ≤ 0.1.
