Hemophilia B, also known as Christmas disease, arises from mutations in the factor
IX (F9) gene. Its treatment in humans, by recombinant protein substitution, is expensive,
thus limiting its application to intermittent treatment in bleeding episodes and prophylaxis
during surgery; development of inhibitory antibodies is an associated hazard. This
study demonstrates permanent therapeutic correction of his disease without development
of immune reactions by introduction of an HIV-based lentiviral vector encoding the
human factor IX protein into the fetal circulation of immunocompetent hemophiliac
and normal outbred mice. Plasma factor IX antigen remained at around 9%, 13%, and
16% of normal in the 3 hemophilia B mice, respectively, until the last measurement
at 14 months. Substantial improvement in blood coagulability as measured by coagulation
assay was seen in all 3 mice and they rapidly stopped bleeding after venipuncture.
No humoral or cellular immunity against the protein, elevation of serum liver enzymes,
or vector spread to the germline or maternal circulation were detected.