Efficient expression of naked DNA delivered intraarterially to limb muscles of nonhuman primates

We have previously shown that the intraarterial delivery of naked plasmid D NA (pDNA) into the femoral artery of rats leads to high levels of foreign g ene expression throughout the muscles of the hindlimb. The present study sh ows that the procedure can also enable high levels of foreign gene expressi on throughout the limb skeletal muscles in rhesus monkeys. The average luci ferase expression in the target muscle was 991.5 +/- 187 ng/g for the arm a nd 1692 +/- 768 ng/g for the leg; compared with 780 ng/g in rat hindlimb. L arge numbers of beta -galactosidase-positive myofibers were found in both l eg and arm muscles, ranging from less than 1% to more than 30% in various m uscles, with an average of 6.9%. The nonhuman primates tolerated the proced ure without significant adverse effects in skeletal muscles, arteries, or o ther organs. Other studies in immunosuppressed rats indicated that stable e xpression is possible. These results suggest that the procedure is likely t o enable efficient and stable gene expression in human muscle without subst antial toxicity.