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通过裸DNA注射和肌肉电穿孔实现高效且受调控的促红细胞生成素生产。

Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation.

作者信息

Rizzuto G, Cappelletti M, Maione D, Savino R, Lazzaro D, Costa P, Mathiesen I, Cortese R, Ciliberto G, Laufer R, La Monica N, Fattori E

机构信息

Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Rome, Italy.

出版信息

Proc Natl Acad Sci U S A. 1999 May 25;96(11):6417-22. doi: 10.1073/pnas.96.11.6417.

Abstract

We show that an electric treatment in the form of high-frequency, low-voltage electric pulses can increase more than 100-fold the production and secretion of a recombinant protein from mouse skeletal muscle. Therapeutical erythopoietin (EPO) levels were achieved in mice with a single injection of as little as 1 microgram of plasmid DNA, and the increase in hematocrit after EPO production was stable and long-lasting. Pharmacological regulation through a tetracycline-inducible promoter allowed regulation of serum EPO and hematocrit levels. Tissue damage after stimulation was transient. The method described thus provides a potentially safe and low-cost treatment for serum protein deficiencies.

摘要

我们表明,以高频、低电压电脉冲形式进行的电处理可使小鼠骨骼肌中重组蛋白的产生和分泌增加100倍以上。单次注射低至1微克的质粒DNA就能使小鼠达到治疗性促红细胞生成素(EPO)水平,并且EPO产生后血细胞比容的增加是稳定且持久的。通过四环素诱导型启动子进行的药理调节可调控血清EPO和血细胞比容水平。刺激后的组织损伤是短暂的。因此,所描述的方法为血清蛋白缺乏症提供了一种潜在安全且低成本的治疗方法。

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