Fig. 3: QMP engineering extends the plasma half-life of FIX-HSA.
a Illustration of the extra- and intra-vascular storages of FIX. Infused and endogenous FIX may relocate from the circulation to the extravascular space where it associates with Col4. The K5A and K5R substitutions in FIX weakens or strengthens its interaction with Col4, respectively. b Illustration of the half-life study in Tg32 mice where 2 mg/kg of FIX-HSA were administered by I.V. injection. Protein quantification was performed by ELISA. The results are presented as (c), protein concentration 24 h after administration and (d), percentage remaining in plasma at each time point compared to day 1 (= 100%), with plasma half-life values to the right, and represent the group mean ± SD of biological replicates (n = 5). e Illustration of the half-life study in FIXplus Balb/c mice where 2.5 mg/kg of FIX-HSA was administered by I.V. injection. Protein quantification was performed by ELISA. The results are presented as (f), protein concentration 24 h after administration and (g), percentage remaining in plasma at each time point compared to day 1 (= 100%), with plasma half-life values to the right, and represent the group mean ± SD of biological replicates (n = 5). Statistical significance was tested by unpaired two-tailed Student’s t tests with 95% confidence level (n = 5; precise p-values are given in Supplementary Tables 2–5). FIX-HSAWT, black; FIXKA-HSAWT, blue; FIXKR-HSAWT, orange; Padua-HSAQMP, gray; PaduaKA-HSAQMP, pink; PaduaKR-HSAQMP, purple. Source data are provided as a Source Data file. a, b, e Created in BioRender. Hovden Aaen, K. (2025) https://BioRender.com/auh41ln.
