Journal
MOLECULAR THERAPY
Volume 2, Issue 3, Pages 204-210Publisher
ACADEMIC PRESS INC
DOI: 10.1006/mthe.2000.0117
Keywords
blood; circulation; electrotransfer; electric pulse-mediated gene transfer; gene therapy; gene transfer; human Factor IX; secreted human placental alkaline phosphatase; skeletal muscle
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Numerous diseases are linked to the absence or insufficient concentration of a specific plasma protein. Gene transfer is an appealing strategy for correction of such diseases. We report high and sustained plasma secretion of human secreted alkaline phosphatase and of human Factor IX by skeletal muscle of mice. This was obtained by delivering square-wave unipolar electric pulses of low field strength (200 V/cm) and long duration (20 ms) to skeletal muscle previously injected with plasmid DNA encoding for the secreted protein. This intramuscular electrotransfer method allows 30- to 150-fold increase in reporter protein secretion, compared to simple plasmid DNA injection. This increase allows one to obtain values of up to 2200 ng/ml of a reporter circulating protein. Moreover, this high level of secretion remains stable for several months.
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