[Non-viral gene transfer results in therapeutic factor IX levels in haemophilia B mice].
Safety issues concerning the risk of malignancy formation and immune response to viral vectors were raised in initial gene therapy trials. In contrast, non-viral gene delivery methods have long been offside. We therefore explore a non-viral gene transfer approach for the treatment of hemophilia B.


METHODS
First, we constructed a strong liver-specific expression plasmid for human factor IX (FIX). Next, we tested the vector by injecting two doses under hydrodynamic conditions into the tail veins of FIX knockout mice.


RESULTS
A single injection resulted in an increase in FIX expression over 100% of normal plasma levels. The FIX resulted fully functional. Further, no anti-FIX antibodies were observed and expression levels were vector dose dependent.


CONCLUSIONS
The high expression obtained in small animals give hope for further development of non-viral gene transfer for the treatment of hemophilia B in humans.
Schüttrumpf
J
J
DRK-Blutspendedienst Baden Württemberg - Hessen gGmbH, Institut für Transfusionsmedizin und Immunhämatologie, Klinikum der Johann Wolfgang Goethe Universität, Sandhofstr. 1, 60528 Frankfurt am Main, Germany. j.schuettrumpf@blutspende.de
Milanov
P
P
Roth
S
S
Seifried
E
E
Tonn
T
T
D000818:Animals; D005164:Factor IX / Q000235:genetics* / Q000378:metabolism*; D005171:Factor X Deficiency / Q000235:genetics* / Q000628:therapy*; D018014:Gene Transfer Techniques; D002836:Hemophilia B / Q000235:genetics* / Q000628:therapy; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010957:Plasmids; D012449:Safety
D005164:Factor IX