Figure 5. Effects of unsaturated and carboxy-terminated lipid structures.

a, Schematic structural representations of the siRNA-lipid conjugates with varied lipid chemistries. b, Cy5-labeled siRNA-lipid conjugates were delivered (1 mg/kg) i.v. Intravascular Cy5 fluorescence measured over approximately 1h was used to calculate siRNA circulation half-life (left panel). Cy5 fluorescence in kidneys, lungs, liver, spleen, and heart was measured 1h after treatment. Fluorescence values in kidneys relative to the total fluorescence values of all organs combined is shown (right panel). c, Size exclusion chromatographic calculation of fraction of Cy5 fluorescence associated with albumin-containing plasma fractions (left panel). Representative in vitro binding responses of siRNA conjugates to human serum albumin (400 nM) measured by biolayer interferometry (right panel). d, Schematic showing treatment schedule for i.v. delivery of siRNA-lipid conjugates. e, Tumors collected on day 7 were dissociated, and tumor cells were assessed for Cy5 fluorescence by flow cytometry (left panel) or lysed and assessed for luciferase activity (right panel). Each bar represents the average value (± S.D.), and each point represents values measured for each independent tumor sample. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001