Figure 2.

Engineered SRC.IDO treatment alters metabolite levels up to 96 h post-injection

(A–E) Naive C57BL/6 mice were injected i.v. with 0.5 mg/kg of LNP A-formulated mRNA and then monitored 6–192 h post-injection. Human IDO1 expression was determined in the (A, B, and D) liver and (A, C, and E) spleen. (A) Representative images of liver and spleen from a V5-tagged SRC.IDO-treated mouse at the indicated time stained with anti-V5 for IDO1 expression compared with PBS-treated controls. Scale bars indicate 100 μm. (B and C) IDO1 expression was determined as percentage of cells positive for V5 tag from (A) in (B) liver and (C) spleen. (D and E) Human IDO1 expression was determined in (D) liver and (E) spleen by ELISA. Dotted line indicates the levels found in PBS-treated or untreated samples.

(F–H) KYN (F) and TRP (G) levels and KYN:TRP ratios (H) were measured in serum by ELISA. Data are mean and SD of n = 5 mice/group and representative of 5 similar experiments. Significance was determined by two-way ANOVA between SRC.IDO and Dead SRC.IDO, followed by Sidak’s multiple comparisons test. ∗p < 0.05, ∗∗p < 0.005,∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.

See also Figures S1–S3.