Fig. 3: Optimization of the headgroup and screening of Library 2. | Nature Communications

Fig. 3: Optimization of the headgroup and screening of Library 2.

From: In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors

Fig. 3

a A workflow for the synthesis and evaluation of Library 2. b In vitro mLuc expression (n = 3 biologically independent samples). HepG2 cells were treated with mLuc-loaded LNPs at an mRNA dose of 15 ng/well (0.24 nM) for 24 h. Data are presented as mean ± SD. c In vivo mLuc expression (n = 3 biologically independent samples). Mice were i.v. injected with mLuc-loaded LNPs at an mRNA dose of 0.1 mg/kg. BLI was performed at 4 h post-treatment and total flux was quantified. Efficacious DB-lipidoids and their amines are highlighted in red. The grey shadow indicates background level. Data are presented as mean ± SD. Statistical significance was evaluated by a one-way ANOVA with Tukey’s correction. d Correlation between in vitro and in vivo results of DB-lipidoids. The black dashed line indicates 10,000 RLU in vitro. The blue dashed line indicates the performance of MC3 LNP in vivo. Statistical significance was evaluated by a two-tailed correlation analysis using GraphPad Prism 8.0. e Structures of efficacious amines and DB-lipidoids. The chemical structure of lead DB-lipidoid 11-10-8 is shown. 11-10-8 demonstrates a total carbon number of 18, a symmetry of 1, and a packing parameter (P) of 4.1. Source data are provided as a Source Data file.

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