cLNPs deliver small RNAs that change gene expression in CD8+ T cells. (A) Structure of ionizable lipid 11-A-M, top performing cLNP from screen 1 and structure of ionizable lipid 1-A-N, top performing cLNP from screen 2. B) Molar composition and characteristics of 11-A-M and 1-A-N. (C) Normalized GFP expression in splenic CD3+ T cells 72 hours after treatment of 2 cLNP carrying siLuc at a dose of 1.5 mg / kg or siGFP at doses of 1.5 mg / kg. (D) Normalized GFP MFI in splenic CD3+ T cells 72 hours after treatment of cLNP carrying either siLuc or siGFP at various doses. One-way ANOVA, *P<0.05. (E) Normalized GFP MFI in splenic CD8+ and CD4+ T cells 72 hours after treatment of cLNP carrying siGFP at a dose of 2.0 mg / kg. unpaired 2-tail t-test, **P<0.01. (F) Normalized GFP MFI in splenic CD3+ T cells as well as CD8+ and CD4+ T cells after treatment of cLNPs carrying sgRNA at a dose of 2.0 mg / kg. Two-way ANOVA, *P<0.05, **P<0.01. (G) Transmission electron microscopy image of 11-A-M formulated to carry siGFP.