HIGH EXPRESSION OF NAKED PLASMID DNA IN MUSCLES OF YOUNG RODENTS

There is a time window at 2 weeks of age for achieving very high level s of foreign gene expression from the intramuscular injection of naked plasmid DMA in mice and rats, The highest expression, over 1 mu g of luciferase protein/muscle, was obtained in Balb/C mice using construct s containing the CMV promoter, a chimeric intron and the luc(+) lucife rase gene, Approximately 50% of the myofibers were intensely blue foll owing the intramuscular injection of a beta-galactosidase expression v ector in 2 week old Balb/C mice, The effects of age, mouse strain and construct were multiplicative, resulting in >1000-fold greater lucifer ase and similar to 20-fold more beta-galactosidase-positive cells. The se high levels of expression were unstable and were not observed in la rger animals (dog, rhesus monkey), These results indicate that enormou s levels of foreign gene expression can be obtained in muscle with nak ed DNA in vivo and will enable the temporary effects of gene function and expression in rodent muscle to be expeditiously studied.