Injection Of Naked Plasmid DNA Research Articles

Intramuscular injection of plasmid DNA.

Striated muscle has recently been shown to be an excellent target tissue for gene transfer in vivo. Both skeletal and cardiac muscle are post-mitotic highly stable structures; consequently gene transfer into these tissues produces long-lasting gene expression. A number of gene transfer systems work effectively with skeletal muscle, including retroviral gene vectors (Dunckley et al., 1993) and adenoviral vectors (Ragot et al., 1993) but the simplest method is the direct injection of naked plasmid DNA into the muscle. Gene uptake and expression following in vivo transfection with plasmid DNA is substantially higher in striated muscle compared with any other tissue (Acsadi et al., 1991a). This methodology, first reported by Wolff and coworkers (1990), has attracted considerable interest as a means of in vivo gene therapy for a wide range of diseases. Skeletal muscle can serve as a platform for systemic gene expression; for example the production of Factor VIII for the treatment of hemophilia A, as well as being the target for treatment, as in the case of Duchenne muscular dystrophy. Plasmid DNA can also be used as a means of delivering genetic vaccination, an approach that potentially can give rise to effective long-lasting humoral and cell-mediated immunity following a single treatment (see Chapter 18).