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Gene therapy has so far been hampered by the methods used to transfer DNA. But electroporation might overcome the problems associated with using a viral vector or simple DNA injection for the treatment of liver damage, suggests Japanese research.
The researchers transferred 50 μg rat hepatocyte growth factor in a modified pKSCX plasmid into the skeletal muscle of 8 week old female mice by electroporation, using a pulse generator. Four days later carbon tetrachloride was used to induce acute liver injury. ELISA was used to determine plasma HGF every other day for three weeks, starting four days after transfer. A fluorescent green plasmid was also transferred to check how effective electroporation had been.
Strong green fluorescence was evident in the muscle where the fluorescent protein had been transferred. HGF was up to four times as high as levels before transfer, peaking at six to nine days and then rapidly diminishing over the three weeks of the study. And hepatocyte apoptosis more than doubled after two days and ALT activity was significantly higher—and took longer to return to normal—in mice not given gene therapy.
The authors point out that, unlike simple DNA injection, electroporation works equally well in regenerating and in normal muscle tissues. And unlike viral vectors, it does not seem to activate an immune response or be mutagenic. The effects of electroporation can also be sustained using repeated transfer.
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