F9 and medical procedure: For intravenous administration of the tS variants in mice, we used LUNAR LNPs, which are similar to those recently established for administration of human factor IX (F9) mRNA in a mouse model of liver haemophilia B21, with a total lipid-to-RNA weight ratio of 25:1 (LUNAR_2021-1, hereafter referred to LUNAR1) (Supplementary Table 3).