High-efficiency gene transfer into skeletal muscle mediated by electric pulses

Lluis M. Mir*, Michel F. Bureau, Julie Gehl, Ravi Rangara, Didier Rouy, Jean Michel Caillaud, Pia Delaere, Didier Branellec, Bertrand Schwartz, Daniel Scherman

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review


    Gene delivery to skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. However, present DNA delivery technologies have to be improved with regard to both the level of expression and interindividual variability. We report very efficient plasmid DNA transfer in muscle fibers by using square- wave electric pulses of low field strength (less than 300 V/cm) and of long duration (more than 1 ms). Contrary to the electropermeabilization-induced uptake of small molecules into muscle fibers, plasmid DNA has to be present in the tissue during the electric pulses, suggesting a direct effect of the electric field on DNA during electrotransfer. This i.m. electrotransfer method increases reporter and therapeutic gene expression by several orders of magnitude in various muscles in mouse, rat, rabbit, and monkey. Moreover, i.m. electrotransfer strongly decreases variability. Stability of expression was observed for at least 9 months. With a pCMVFGF1 plasmid coding for fibroblast growth factor 1, this protein was immunodetected in the majority of muscle fibers subjected to the electric pulses. DNA electrotransfer in muscle may have broad applications in gene therapy and in physiological pharmacological, and developmental studies.

    Sider (fra-til)4262-4267
    Antal sider6
    TidsskriftProceedings of the National Academy of Sciences of the United States of America
    Udgave nummer8
    StatusUdgivet - 13 apr. 1999


    Udforsk hvilke forskningsemner 'High-efficiency gene transfer into skeletal muscle mediated by electric pulses' indeholder.