Accumulation of human apolipoprotein-E in rat plasma after in vivo intramuscular injection of naked dna

Vito M. Fazio, Sergio Fazio, Monica Rinaldi, M. Valeria Catani, Sergio Zotti, Silvia A. Ciafre, Davide Seripa, Giorgio Ricci, Maria Giulia Farace

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    24 Scopus citations

    Abstract

    Naked DNA was found to be incorporated and consistently expressed after in vivo direct injection into striated muscle. In addition to the local expression of muscle-related or exogenous proteins, intramuscular direct gene transfer may be a useful tool to deliver recombinant proteins into the blood stream. However, no direct demonstration of recombinant protein secretion from muscle to the circulation has been reported thus far. We have injected a naked plasmid DNA containing the human receptor-binding defective apo-E2 cDNA, under the control of CMV promoter, into the quadriceps of Yoshida rats, affected by hereditary hypercholesterolemia and altered LDL-receptor activity. Plasma accumulation of human apo-E2 was demonstrated for at least 45 days after injection. On the contrary, the expression of the normal human apo-E3, injected into the muscle of normal Wistar rats, was demonstrated only in the area of muscular injection and not in the blood plasma. Endogenous rat apo-E expression was not affected by the exogenous human apo-E2 production. Our results demonstrate the availability of intramuscular direct gene transfer as a safe and simple method for the chronic systemic delivery of recombinant proteins to the circulation, although further improvements are needed in order to enhance the efficiency and stability of expression.

    Original languageEnglish (US)
    Pages (from-to)298-305
    Number of pages8
    JournalBiochemical and Biophysical Research Communications
    Volume200
    Issue number1
    DOIs
    StatePublished - Apr 15 1994

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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  • Cite this

    Fazio, V. M., Fazio, S., Rinaldi, M., Catani, M. V., Zotti, S., Ciafre, S. A., Seripa, D., Ricci, G., & Farace, M. G. (1994). Accumulation of human apolipoprotein-E in rat plasma after in vivo intramuscular injection of naked dna. Biochemical and Biophysical Research Communications, 200(1), 298-305. https://doi.org/10.1006/bbrc.1994.1448