Enhancement of naked FIX minigene expression by chloroquine in mice.

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.

[1]  L. Collins,et al.  The in vivo use of chloroquine to promote non‐viral gene delivery to the liver via the portal vein and bile duct , 2003, The journal of gene medicine.

[2]  N. Paton,et al.  Hydroxychloroquine, hydroxycarbamide, and didanosine as economic treatment for HIV-1 , 2002, The Lancet.

[3]  J. Miyazaki,et al.  High‐level expression of naked DNA delivered to rat liver via tail vein injection , 2002, The journal of gene medicine.

[4]  P. Scheltens,et al.  Effect of hydroxychloroquine on progression of dementia in early Alzheimer's disease: an 18-month randomised, double-blind, placebo-controlled study , 2001, The Lancet.

[5]  J. Mcarthur,et al.  Factors influencing the development of an anti-factor IX (FIX) immune response following administration of adeno-associated virus-FIX. , 2001, Blood.

[6]  R. Levy,et al.  Enhanced plasmid DNA transfection with lysosomotropic agents in cultured fibroblasts. , 2001, International journal of pharmaceutics.

[7]  M. Kay,et al.  Linear DNAs concatemerize in vivo and result in sustained transgene expression in mouse liver. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[8]  H. Ginsburg,et al.  An integrated model of chloroquine action. , 1999, Parasitology today.

[9]  Dexi Liu,et al.  Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA , 1999, Gene Therapy.

[10]  J. Wolff,et al.  High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA. , 1999, Human gene therapy.

[11]  T. Keller,et al.  Fatal chloroquine intoxication. , 1998, Forensic science international.

[12]  M. Imperiale,et al.  Promoter Attenuation in Gene Therapy: Interferon-γ and Tumor Necrosis Factor-α Inhibit Transgene Expression , 1997 .

[13]  F. Yull,et al.  Mammalian cDNA and prokaryotic reporter sequences silence adjacent transgenes in transgenic mice. , 1997, Nucleic acids research.

[14]  K Zatloukal,et al.  Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G. Padmanaban,et al.  Chloroquine inhibits heme-dependent protein synthesis in Plasmodium falciparum. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Mechtler,et al.  Transferrin-polycation-mediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Cotten,et al.  Receptor-mediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoietic cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P. Schlesinger,et al.  A perspective on antimalarial action: effects of weak bases on Plasmodium falciparum. , 1986, Biochemical pharmacology.

[19]  M. Kay,et al.  Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.