Fig. 1: Cascade amplifications of therapeutic payloads encoding mouse IL-12 on B16F10 melanoma therapy.

a Illustration of the cascade amplification of therapeutic payloads (CATP) was created in BioRender. Li, Y. (2025) https://BioRender.com/g50p020. b Illustrations of constructs for CATP. c Effects of CATP in HEK293 cells. HEK293 cells were treated by LNP encapsulated SamRNA mRNA encoding with eGFP and modified mRNA encoding with envelop and capsids from VEE or LNP encapsulated SamRNA mRNA encoding with eGFP and modified mRNA encoding firefly luciferase. Then the GFP percentages were determined by flow cytometer at days 1, 2, 3, and 4 post transfection. The shown are the changes of GFP versus days post transfection. d Scheme of tumor inoculation and treatment: Six- to eight-week-old C57BL/6 mice (n = 5 per group, a cage of animal) were subcutaneously inoculated with 1 million B16F10 melanoma cells. Seven days post-inoculation, mice were intratumorally treated with PBS (Control group of basal line), or LNP encapsulating 10 µg SamRNA encoding with mouse IL-12 (mIL-12) and 1 µg modified mRNA encoding with firefly luciferase (Control group of treated group) or LNP encapsulated 10 µg of SamRNA encoding mIL-12¹² and 1 µg modified mRNA encoding capsids/envelops from VEE, following the principle that molar ratio of modified mRNA (1 µg) is smaller than it of samRNA (10 µg). e mIL-12 expression in sera and tumors. The P-Values labeled in e were determined by Tukey’s multiple comparisons test.