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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Calcium electrotransfer for termination of transgene expression in muscle

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  1. Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin

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  2. Physiological effects of high- and low-voltage pulse combinations for gene electrotransfer in muscle

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Gene electrotransfer is expanding in clinical use, thus we have searched for an emergency procedure to stop transgene expression in case of serious adverse events. Calcium is cytotoxic at high intracellular levels, so we tested effects of calcium electrotransfer on transgene expression in muscle. A clinical grade calcium solution (20 μl, 168 mM) was injected into transfected mouse or rat tibialis cranialis muscle. Ca(2+) uptake was quantified using calcium 45 ((45)Ca), and voltage and time between injection and pulsation were varied. Extinction of transgene expression was investigated by using both in vivo imaging of infrared fluorescent "Katushka" and erythropoietin evaluated by ELISA and hemoglobin. Histology was performed. Electrotransfer of Katushka and erythropoietin yielded significant expression. Maximal calcium uptake occurred after injection of Ca(2+) before electropulsing using eight high voltage pulses of 1000 V/cm. Using these parameters, in vivo imaging showed that transgene expression significantly decreased 4 hr after Ca(2+) electrotransfer and was eliminated within 24 hr. Similarly, serum erythropoietin was reduced by 46% at 4 hr and to control levels at 2 days. Histological analyses showed muscle damage and subsequent regeneration. Electrotransfer of isotonic CaCl(2) terminates transgenic protein expression in muscles and may be used for contingency elimination of transgene expression.
Original languageEnglish
JournalHuman Gene Therapy
Volume22
Issue number6
Pages (from-to)753-60
Number of pages8
ISSN1043-0342
DOIs
Publication statusPublished - 2011

    Research areas

  • Animals, Calcium, Electroporation, Erythropoietin, Gene Expression, Gene Therapy, Gene Transfer Techniques, Mice, Mice, Inbred C57BL, Muscles, Rats, Rats, Wistar, Transgenes

ID: 33271578