Fig. 3: Robust tumor accumulation and tumor gene silencing using si < (EG18L)2.
a–d Mice bearing intra-mammary MDA-MB-231.Luc tumors were treated with siRNA-lipid conjugates, or free siRNA, using a siRNA sequence against luciferase (siLuc). a Schematic showing treatment schedule for i.v. delivery of siRNA-lipid conjugates, or free siRNA, to tumor-bearing mice. b Cy5 fluorescence tumor:kidney ratio for each mouse as measured on day 7 (18 h after injection with fluorescent siRNA) (n = 5–9). c Luciferase activity was measured in tumor lysates collected on treatment day 7. Bars show the average (± S.D.) tumor luciferase per group, and points are the values for each tumor (assessed in triplicate) (n = 5–9). All values shown are relative to the average luciferase activity of saline-treated controls, which was set to a value of 1. d Tumors were assessed by IHC analysis for firefly luciferase (green). Nuclei were counterstained with DAPI (blue). Representative images are shown (e, f). Mice bearing intra-mammary MDA-MB-231 tumors were treated one time with si < (EG18L)2, using siRNA sequences against MCL1 (siMCL1) at increasing doses (2.5 mg/kg–20 mg/kg). Tumors were assessed on treatment day 4 and day 8. e Schematic showing i.v. delivery of siRNA-lipid conjugates, or free siRNA, to tumor-bearing mice. f Human MCL1 mRNA levels measured in whole tumor RNA collected on treatment day 4 (left panel) and day 8 (right panel). Bars show the average (± S.D.), and points are the values for an individual tumor (assessed in triplicate) (n = 5–6). All values shown are relative to values measured with saline controls, which were set to a value of 1. For (b, c), significance was determined using one-way ANOVA with Dunnetts’s multiple comparisons test using the siRNA and saline groups for comparison, respectively. For (f), significance was determined using one-way ANOVA with Tukey’s multiple comparisons test.
