Enhancement of naked FIX minigene expression by chloroquine in mice

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:gzhp
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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 g of pCMV-hFIX and chloroquine (0, 100, 200, and 500 mol/L) in 2.2 mL of Ringer solution within 6-7 s, the level andstability of hFIX expression, liver damage and toxicity were then examined. RESULTS: The maximum expression ofhFIX level was 4.41.8 mg/L at 8 h after injection, 9.71.6 mg/L at 24 h only existed in 200 mol/L chloroquine-treated animals, which is 3-4 fold higher than that of control (P<0.01). There is no significant difference observedamong all the treated groups, 3 d later. Transaminase level and liver histological study showed the damage of liverwas not related to chloroquine (P>0.05). CONCLUSION: Chloroquine can enhance and sustain exogenous geneexpression in vivo without side effect under our experimental conditions. METHODS: Hydrodynamics-based naked DNA plasmid administration was performed by tail vein injection of 10 g of pCMV-hFIX and chloroquine (0, 100 , 200, and 500 mol / L) in 2.2 mL of Ringer solution within 6-7 s, the level and ability of hFIX expression, liver damage and toxicity were then examined. RESULTS: The maximum expression of hFIX level was 4.41.8 mg / L at 8 h after injection, 9.71.6 mg / L at 24 h only existed in 200 mol / 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.
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