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Biodistribution and blood clearance of plasmid DNA administered in arginine peptide complexes

机译:精氨酸肽复合物中施用的质粒DNA的生物分布和血液清除

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Background Peptide/DNA complexes have great potential as non-viral methods for gene delivery. Despite promising results for peptide-mediated gene delivery technology, an effective systemic peptide-based gene delivery system has not yet been developed. Methods This study used pCMV-Luc as a model gene to investigate the biodistribution and the in vivo efficacy of arginine peptide-mediated gene delivery by polymerase chain reaction (PCR). Results Plasmid DNA was detected in all organs tested 1 h after intraperitoneal administration of arginine/DNA complexes, indicating that the arginine/DNA complexes disseminated widely through the body. The plasmid was primarily detected in the spleen, kidney, and diaphragm 24 h post administration. The mRNA expression of plasmid DNA was noted in the spleen, kidney, and diaphragm for up to 2 weeks, and in the other major organs, for at least 1 week. Blood clearance studies showed that injected DNA was found in the blood as long as 6 h after injection. Conclusions Taken together, our results demonstrated that arginine/DNA complexes are stable in blood and are effective for in vivo gene delivery. These findings suggest that intraperitoneal administration of arginine/DNA complexes is a promising tool in gene therapy.
机译:背景肽/ DNA复合物作为基因传递的非病毒方法具有巨大的潜力。尽管肽介导的基因递送技术取得了可喜的成果,但尚未开发出有效的基于全身肽的基因递送系统。方法本研究以pCMV-Luc为模型基因,通过聚合酶链反应(PCR)研究精氨酸肽介导的基因传递的生物分布和体内功效。结果腹腔注射精氨酸/ DNA复合物1小时后,在所有测试器官中均检测到质粒DNA,表明精氨酸/ DNA复合物在体内广泛传播。给药后24小时,主要在脾,肾和diaphragm肌中检测到质粒。在脾脏,肾脏和diaphragm肌中记录质粒DNA的mRNA表达长达2周,在其他主要器官中至少持续1周。血液清除研究表明,注射后6小时之内就在血液中发现了注射的DNA。结论综上所述,我们的结果表明精氨酸/ DNA复合物在血液中稳定并且对于体内基因传递有效。这些发现表明,腹膜内施用精氨酸/ DNA复合物是基因治疗中的有前途的工具。

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