FIG. 5.

Intratumoral delivery of MC3-encapsulated PUMA-122ts triggers apoptosis in tumor cells while alleviating liver toxicity. (a) Schematic representation of PUMA mRNA with miR122 target site(s) (122ts or 3 × 122ts) in the 3′ UTR. (b) Schematic representation of PUMA-mediated apoptosis pathway. (c) PUMA-122ts triggers apoptosis in tumor cells while alleviating liver toxicity in a Hep3b subcutaneous xenograft mouse model. Representative images from tumor and liver IHC for CC3, and H&E staining 6 h after intratumoral injection of 6.25-μg PUMA mRNA. Quantification of percentage CC3-positive area in tumor and liver, and ALT and AST levels in serum are shown. NST represents an RNA with a similar sequence where all identifiable start codons AUG, CUG, and GUG have been removed. Error bars represent standard deviation in the figure. Levels generated upon administration of LNP-encapsulated mRNA were compared with levels with buffer, and P values were generated by Prism using one-way analysis of variance. ns P > 0.05, *P < 0.05, ***P < 0.001, ****P < 0.0001. IHC, immunohistochemistry; CC3, cleaved caspase 3; H&E, hematoxylin and eosin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; NST, nonstart RNA.