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• W2100069921 abstract "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. Ca2+ uptake was quantified using calcium 45 (45Ca), 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 Ca2+ 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 Ca2+ 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 CaCl2 terminates transgenic protein expression in muscles and may be used for contingency elimination of transgene expression. In this study, Hojman and colleagues report on a simple and efficient way of quickly eliminating all transgene expression in muscles by calcium electrotransfer. The authors show that the massive influx of calcium during calcium electrotransfer disrupts normal cell function, eliminating transgene expression in mouse and rat muscle following gene transfer by DNA electroporation. According to the authors, this procedure represents a feasible way for the quick elimination of transgene expression in the clinic." @default.
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• W2100069921 date "2011-06-01" @default.
• W2100069921 modified "2023-10-03" @default.
• W2100069921 title "Calcium Electrotransfer for Termination of Transgene Expression in Muscle" @default.
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• W2100069921 doi "https://doi.org/10.1089/hum.2010.209" @default.
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