Enhancement of naked FIX minigene expression by chloroquine in mice.
OBJECTIVE
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).


CONCLUSIONS
Chloroquine can enhance and sustain exogenous gene expression in vivo without side effect under our experimental conditions.
Chen
Hong-yan
HY
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
Zhu
Huan-zhang
HZ
Lu
Bin
B
Xu
Xuan
X
Yao
Ji-hua
JH
Shen
Qi
Q
Xue
Jing-lun
JL
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D005164:Factor IX / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D014162:Transfection
D002738:Chloroquine; D005164:Factor IX; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase