Accumulation of Human Apolipoprotein-E in Rat Plasma After in vivo Intramuscular Injection of Naked DNA

V. M. Fazio, Sergio Fazio, M. Rinaldi, M. V. Catani, S. Zotti, S. A. Ciafre, D. Seripa, G. Ricci, M. G. Farace

Research output: Contribution to journalArticle

24 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Intramuscular Injections
Apolipoprotein E2
Apolipoproteins E
Muscle
Rats
Recombinant Proteins
Gene transfer
Plasmas
DNA
Muscles
Injections
Blood
Apolipoprotein E3
Striated Muscle
LDL Receptors
Direct injection
Hypercholesterolemia
Genes
Wistar Rats
Plasmids

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Accumulation of Human Apolipoprotein-E in Rat Plasma After in vivo Intramuscular Injection of Naked DNA. / Fazio, V. M.; Fazio, Sergio; Rinaldi, M.; Catani, M. V.; Zotti, S.; Ciafre, S. A.; Seripa, D.; Ricci, G.; Farace, M. G.

In: Biochemical and Biophysical Research Communications, Vol. 200, No. 1, 15.04.1994, p. 298-305.

Research output: Contribution to journalArticle

Fazio, V. M. ; Fazio, Sergio ; Rinaldi, M. ; Catani, M. V. ; Zotti, S. ; Ciafre, S. A. ; Seripa, D. ; Ricci, G. ; Farace, M. G. / Accumulation of Human Apolipoprotein-E in Rat Plasma After in vivo Intramuscular Injection of Naked DNA. In: Biochemical and Biophysical Research Communications. 1994 ; Vol. 200, No. 1. pp. 298-305.
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