Efficient expression of naked DNA delivered intraarterially to limb muscles of nonhuman primates
Efficient expression of naked DNA delivered intraarterially to limb muscles of nonhuman primates
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DOI：
10.1089/10430340150504046
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发表时间：
2001-03-01
影响因子：
4.2
通讯作者：
Wolff, JA
中科院分区：
文献类型：
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作者：
Zhang, GF;Budker, V;Wolff, JA
我们以前已经表明，裸质粒DNA（pDNA）到大鼠的股动脉动脉动脉内递送导致整个后肢肌肉的外源基因表达的高水平。目前的研究表明，该程序也可以使高水平的外源基因表达在恒河猴的整个肢体骨骼肌。靶肌肉中的平均荧光素酶表达为991.5 +/- 187 ng/g（手臂）和1692 +/- 768 ng/g（腿部）;而大鼠后肢中为780 ng/g。在腿部和手臂肌肉中均发现大量β-半乳糖苷酶阳性肌纤维，在各种肌肉中从不到1%到超过30%不等，平均为6.9%。非人灵长类动物耐受了该手术，对骨骼肌、动脉或其他器官没有明显的不良影响。在免疫抑制大鼠中的其他研究表明稳定表达是可能的。这些结果表明，该方法可能能够在人类肌肉中有效和稳定地表达基因，而没有实质性的毒性。
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.