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Enhancement of naked FIX minigene expression by chloroquine in mice
Hong-yan Chen1, Huan-zhang Zhu, Bin Lu
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
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.
