Moreover, starting at 3-weeks post-HDTVi, we tested LNP-CTNNB1 at the 1mg/kg dosage in a third CTNNB1-mutated model, the S45Y-mutant-β-catenin-Nrf2-Met (β-N-M) model, which represents ~5% of human HCC, independent of β-N and β-M models.30 Following a similar treatment protocol to the β-M model, we again observed significant tumor responses (Figure 1m–q; Figure S3g–h), similar to the results obtained in the “two-hit” models (β-N and β-M). Here, CTNNB1 is linked to neoplasm.