Fig. 2: Optimization of the tail region and screening of Library 1.

a A workflow for the synthesis and evaluation of Library 1. b In vitro mLuc expression shown in a heat map (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. RLU, relative light unit. Data are presented as mean. c In vivo mLuc expression shown in a heat map (n = 3 biologically independent samples). Mice were i.v. injected with mLuc-loaded LNPs at an mRNA dose of 0.1 mg/kg. Bioluminescence imaging (BLI) was performed at 4 h post-treatment and total flux was quantified. Data are presented as mean. 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 Body tail-activity relationship (n = 3 biologically independent samples). f Branch tail-activity relationship (n = 3 biologically independent samples). g Total carbon number-activity relationship. h Total carbon number-symmetry-activity relationship. The grey shadows indicate background levels. Source data are provided as a Source Data file.