Efficient expression of naked dna delivered intraarterially to limb muscles of nonhuman primates.
We have previously shown that the intraarterial delivery of naked plasmid DNA (pDNA) into the femoral artery of rats leads to high levels of foreign gene expression throughout the muscles of the hindlimb. The present study shows that the procedure can also enable high levels of foreign gene expression throughout the limb skeletal muscles in rhesus monkeys. The average luciferase expression in the target muscle was 991.5 +/- 187 ng/g for the arm and 1692 +/- 768 ng/g for the leg; compared with 780 ng/g in rat hindlimb. Large numbers of beta-galactosidase-positive myofibers were found in both leg and arm muscles, ranging from less than 1% to more than 30% in various muscles, with an average of 6.9%. The nonhuman primates tolerated the procedure without significant adverse effects in skeletal muscles, arteries, or other organs. Other studies in immunosuppressed rats indicated that stable expression is possible. These results suggest that the procedure is likely to enable efficient and stable gene expression in human muscle without substantial toxicity.
Department of Pediatrics and Medical Genetics, Waisman Center, Medical School, University of Wisconsin-Madison, 53705, USA.
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Zhang
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Budker
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Williams
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Subbotin
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Wolff
D000818:Animals; D004247:DNA / Q000235:genetics*; D005263:Femoral Artery; D015870:Gene Expression; D005822:Genetic Vectors; D006066:Gonads / Q000201:enzymology*; D006614:Hindlimb; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008253:Macaca mulatta; D018482:Muscle, Skeletal / Q000201:enzymology*; D009152:Mutagenicity Tests; D010957:Plasmids / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D004247:DNA; D008156:Luciferases; D001616:beta-Galactosidase