Inducible production of erythropoietin using intramuscular injection of block copolymer/DNA formulation.

摘要: Background We have previously shown that intramuscular injection of plasmid DNA formulated with a non-ionic amphiphile synthetic vector [poly(ethylene oxide)13-poly(propylene oxide)30-poly(ethylene oxide)13 block copolymer; PE6400] increases reporter gene expression compared naked DNA. We now investigated this simple non-viral formulation for production secreted proteins from the mouse skeletal muscle. Methods Plasmids encoding either constitutive human alkaline phosphatase or murine erythropoietin inducible via Tet-on system were PE6400 and intramuscularly injected into tibial anterior muscle. Results PE6400/DNA led to an increased amount recombinant muscle as In presence doxycycline, single 10µg significantly hematocrit, whereas same in absence had no effect. The increase hematocrit was stable 42 days. tetracycline-inducible promoter permitted pharmacological control level after injection. However, 4 months post-injection returned its pre-injection value, even doxycycline. This phenomenon likely caused by immune response against tetracycline-activated transcription factor. Conclusions Intramuscular provides efficient method secretion non-muscle proteins. Copyright © 2004 John Wiley & Sons, Ltd.