MYOSIN REGULATORY ELEMENTS AS VECTORS FOR GENE-TRANSFER BY INTRAMUSCULAR INJECTION

Intramuscular injection of plasmid constructs promises to be an effect ive way of carrying out gene therapy for muscle disorders as well as u sing muscle as an in vivo expression system for disorders that involve the gene product being secreted into the bloodstream. The effectivene ss of this method depends on the design of the cassette used for the e xpression of the cDNA of the introduced gene. We tested the levels of expression achieved by a number of muscle-specific promoters and a myo sin light chain enhancer when spliced to the reporter gene chloramphen icol acetyltransferase (CAT), in vitro and in vivo by injection into f ast and slow muscles of the mouse, The results show that the highest l evels of expression ape achieved by a combination of a truncated myosi n heavy chain promoter and the enhancer, and that a whole range of exp ression levels is obtained with the other combinations tested. The dat a show that a cassette based on these elements should provide efficien t vectors for the introduction and expression of genes following intra muscular injection of naked DNA.