Enhancement of naked FIX minigene expression by chloroquine in mice

Acta Pharmacol Sin. 2004 May;25(5):570-5.

Abstract

Aim: To study the effect of chloroquine on the expression of human clotting factor IX (hFIX) in mice.

Methods: Hydrodynamics-based naked DNA plasmid administration was performed by tail vein injection of 10 microg of pCMV- hFIX and chloroquine (0, 100, 200, and 500 micromol/L) in 2.2 mL of Ringer's solution within 6-7 s, the level and stability of hFIX expression, liver damage and toxicity were then examined.

Results: The maximum expression of hFIX level was 4.4+/-1.8 mg/L at 8 h after injection, 9.7+/-1.6 mg/L at 24 h only existed in 200 micromol/L chloroquine-treated animals, which is 3-4 fold higher than that of control (P<0.01). There is no significant difference observed among all the treated groups, 3 d later. Transaminase level and liver histological study showed the damage of liver was not related to chloroquine (P>0.05).

Conclusion: Chloroquine can enhance and sustain exogenous gene expression in vivo without side effect under our experimental conditions.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Chloroquine / pharmacology*
  • Factor IX / genetics*
  • Factor IX / metabolism
  • Gene Expression / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Plasmids / administration & dosage
  • Plasmids / genetics*
  • Transfection

Substances

  • Chloroquine
  • Factor IX
  • Aspartate Aminotransferases
  • Alanine Transaminase