Persistence of expression and tolerance of exogenous and expressed hFIX.

Prenatal and adult mice were given an initial intravenous injection of AdhFIX and were then repeatedly rechallenged, as adults, with intraperitoneal hFIX protein then intravenous AdhFIX while hFIX concentrations were measured. The y-axis shows blood hFIX concentrations (microgram per milliliter) after in utero or adult injection of AdhFIX (phase 1), after repeated injection of hFIX protein to the adult mice (phase 2, shaded), and after repeated injection of AdhFIX to the adult mice (phase 3). The x-axis shows the experimental time course in days after first the injection (day 0). Arrowheads indicate injection points. The D15 and D17 fetal AdhFIX group are mice initially injected in utero with AdhFIX at days 15 or 17 after conception, respectively. The adult AdhFIX group contains mice initially injected intravenously with AdhFIX as adults. The protein challenge control group did not receive prior injection of AdhFIX. The AdhFIX challenge group received neither prior injections of AdhFIX nor hFIX protein. The D15 and D17 fetal AdhFIX groups, the adult AdhFIX group, and the protein challenge control group received their first hFIX protein injection at 66, 56, 16 to 18, and 30 to 35 weeks of age, respectively. Diamonds show the analysis of individual mice at a given time point. The number of samples with no detectable hFIX at each time point is depicted as a diamond and number, both lying beneath the lower dotted line. The first 2 time points (days 2 and 9) are mice from the D15 fetal AdhFIX group killed for analysis; the ensuing points are from continuous sampling of mice in all groups. The reduction of animals over the length of time was predominantly age-related death.