The Advances of Hepatocyte-Directed Gene Transfer Vectors_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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The Second Department of General Surgery, The First Clinical Medical College,Harbin University of Medical Sciences，Harbin 150001;

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Keywords：

Hepatocyte; Gene therapy; Gene transfer vector

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Objective To investigate the stable, high effective and low toxicity gene transfer vectors’ basics in research and clinical application.
Methods Current status of hepatocytedirected gene transfer vectors were reviewed by history document and contemporary experimental advances analysis.
Results Viral and nonviral vector systems could both transduce target genes to liver effectively with various transduction rates based on their corresponding biological characteristics.
Conclusion Hepatocyte is the effective target for gene therapy of liverrelated genetic, neoplastic and infectious diseases, although the security needs to be further evaluated.

Citation： DAI Wenjie,JIANG Hongchi. The Advances of Hepatocyte-Directed Gene Transfer Vectors. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2002, 9(1): 58-60. doi: Copy

1.	Ferry N, Heard JM. Liverdirected gene transfer vectors [Ｊ]. Hum Gene Ther, 1998； 9(9)∶1975.
2.	Grossman M, Rader DJ, Muler DWM, et al. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolemia [Ｊ]. Nature Med, 1995; 1(10)∶1148.
3.	Kitten O, Cosset FL, Ferry N. Highly efficient retrovirusmediated gene transfer into rat hepatocytes in vivo [Ｊ]. Hum Gene Ther, 1997; 8(7)∶1491.
4.	Tada K, Chowdhury NR, Neufeld D, et al. Longterm reduction of serum bilirubin levels in Gunn rats by retroviral gene transfer in vivo [Ｊ]. Liver Tansplant Surg, 1998; 4(1)∶ 78.
5.	Shiraishi M, Tomori H, Nagahama M, et al. Stable gene expression with VSVG pseudotypedretrovirus vector in the rat liver [Ｊ]. J Surg Res, 1999; 84(1)∶168.
6.	Jooss K, Yang Y, Wilson JM.Cyclophosphamide diminishes inflammation and prolongs transgene expression following delivery of adenoviral vectors to mouse liver and lung [Ｊ]. Hum Gene Ther, 1996; 7(8)∶1555.
7.	Kay MA, Meuse L, Gown AM, et al. Transient immunomodulation with antiCD40 ligand antibody and CTLA4Ig enhances persistence and secondary adenovirusmediated gene transfer into mouse liver [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(8)∶4686.
8.	Ilan Y, Attavar P, Takahashi M, et al. Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits longterm gene therapy in Gunn rats [Ｊ]. J Clin Invest, 1996; 98(10)∶2640.
9.	Wang Q, Greenburg G, Bunch D, et al. Persistent transgene expression in mouse liver following in vivo gene transfer with a delta E1/delta E4 adenovirus vector [Ｊ]. Gene Ther, 1997; 4(2)∶393.
10.	Dedieu JF, Vigne E, Torrent C, et al. Longterm gene delivery into the livers of immunocompetent mice with E1/E4defective adenoviruses [Ｊ]. J Virol, 1997; 71(5)∶4626.
11.	Bruder JT, Jie T, McVey DL, et al. Expression of gp19k increases the persistence of transgene expression from an adenovirus vector in the mouse lung and liver [Ｊ]. J Virol, 1997; 71(9)∶7623.
12.	Schiedner G, Morral N, Parks RJ, et al. Genomic DNA transfer a high capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity [Ｊ]. Nature Genet, 1998; 18(1)∶180.
13.	Walker SL, Wonderling RS, Owens RA. Mutational analysis of the adenoassociated virus Rep68 protein: identification of critical residues necessary for sitespecific endonuclease activity [Ｊ]. J Virol, 1997; 71(4)∶2722.
14.	Di Pasquale G, Stacey SN. Adenoassociated virus Rep78 protein interacts with protein kinase A and its homolog PRKX and inhibits CREBdependent transcriptional activation [Ｊ]. J Virol, 1998; 72(10)∶7916.
15.	Koeber1 DD, Alexander IE, Halbert CL, et al. Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adenoassociated virus vectors [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(3)∶1426.
16.	Fracfel C, Jaeoby DR, Lage C, et al. Gene transfer into hepatocytes mediated by helper virusfree HSV/AAV hybrid vectors [Ｊ]. Mol Med, 1997; 3(2)∶813.
17.	MartinezFong D, Mullersman JE, Purchio AF, et al. Nonenzymatic glycosylation of polyLlysine: a new tool for targeted gene delivery [Ｊ]. Hepatology, 1994; 20(6)∶1602.
18.	Bandyopadhyay P, Kren BT, Ma X, et al. Enhanced gene transfer into HuHT cells and primary rat hepatocytes using transfer liposomes and polyethylenimine [Ｊ]. Biotechniques, 1998; 25(2)∶ 282.
19.	Ueki T, Kaneda Y, Tsutsui H, et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats [Ｊ]. Nat Med, 1999; 5(2)∶ 226.
20.	Hirano T, Fujimoto J, Ueki T, et al. Persistent gene expression in rat liver in vivo by repetitive transfections using HVJliposomc [Ｊ]. Gene Ther, 1998; 5(3)∶459.
21.	Hara T, Tan Y, Huang L. In vivo gene delivery to the liver using reconstituted chylomicron remnants as a novel nonviral vector [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(23)∶14547.

1. Ferry N, Heard JM. Liverdirected gene transfer vectors [Ｊ]. Hum Gene Ther, 1998； 9(9)∶1975.
2. Grossman M, Rader DJ, Muler DWM, et al. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolemia [Ｊ]. Nature Med, 1995; 1(10)∶1148.
3. Kitten O, Cosset FL, Ferry N. Highly efficient retrovirusmediated gene transfer into rat hepatocytes in vivo [Ｊ]. Hum Gene Ther, 1997; 8(7)∶1491.
4. Tada K, Chowdhury NR, Neufeld D, et al. Longterm reduction of serum bilirubin levels in Gunn rats by retroviral gene transfer in vivo [Ｊ]. Liver Tansplant Surg, 1998; 4(1)∶ 78.
5. Shiraishi M, Tomori H, Nagahama M, et al. Stable gene expression with VSVG pseudotypedretrovirus vector in the rat liver [Ｊ]. J Surg Res, 1999; 84(1)∶168.
6. Jooss K, Yang Y, Wilson JM.Cyclophosphamide diminishes inflammation and prolongs transgene expression following delivery of adenoviral vectors to mouse liver and lung [Ｊ]. Hum Gene Ther, 1996; 7(8)∶1555.
7. Kay MA, Meuse L, Gown AM, et al. Transient immunomodulation with antiCD40 ligand antibody and CTLA4Ig enhances persistence and secondary adenovirusmediated gene transfer into mouse liver [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(8)∶4686.
8. Ilan Y, Attavar P, Takahashi M, et al. Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits longterm gene therapy in Gunn rats [Ｊ]. J Clin Invest, 1996; 98(10)∶2640.
9. Wang Q, Greenburg G, Bunch D, et al. Persistent transgene expression in mouse liver following in vivo gene transfer with a delta E1/delta E4 adenovirus vector [Ｊ]. Gene Ther, 1997; 4(2)∶393.
10. Dedieu JF, Vigne E, Torrent C, et al. Longterm gene delivery into the livers of immunocompetent mice with E1/E4defective adenoviruses [Ｊ]. J Virol, 1997; 71(5)∶4626.
11. Bruder JT, Jie T, McVey DL, et al. Expression of gp19k increases the persistence of transgene expression from an adenovirus vector in the mouse lung and liver [Ｊ]. J Virol, 1997; 71(9)∶7623.
12. Schiedner G, Morral N, Parks RJ, et al. Genomic DNA transfer a high capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity [Ｊ]. Nature Genet, 1998; 18(1)∶180.
13. Walker SL, Wonderling RS, Owens RA. Mutational analysis of the adenoassociated virus Rep68 protein: identification of critical residues necessary for sitespecific endonuclease activity [Ｊ]. J Virol, 1997; 71(4)∶2722.
14. Di Pasquale G, Stacey SN. Adenoassociated virus Rep78 protein interacts with protein kinase A and its homolog PRKX and inhibits CREBdependent transcriptional activation [Ｊ]. J Virol, 1998; 72(10)∶7916.
15. Koeber1 DD, Alexander IE, Halbert CL, et al. Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adenoassociated virus vectors [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(3)∶1426.
16. Fracfel C, Jaeoby DR, Lage C, et al. Gene transfer into hepatocytes mediated by helper virusfree HSV/AAV hybrid vectors [Ｊ]. Mol Med, 1997; 3(2)∶813.
17. MartinezFong D, Mullersman JE, Purchio AF, et al. Nonenzymatic glycosylation of polyLlysine: a new tool for targeted gene delivery [Ｊ]. Hepatology, 1994; 20(6)∶1602.
18. Bandyopadhyay P, Kren BT, Ma X, et al. Enhanced gene transfer into HuHT cells and primary rat hepatocytes using transfer liposomes and polyethylenimine [Ｊ]. Biotechniques, 1998; 25(2)∶ 282.
19. Ueki T, Kaneda Y, Tsutsui H, et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats [Ｊ]. Nat Med, 1999; 5(2)∶ 226.
20. Hirano T, Fujimoto J, Ueki T, et al. Persistent gene expression in rat liver in vivo by repetitive transfections using HVJliposomc [Ｊ]. Gene Ther, 1998; 5(3)∶459.
21. Hara T, Tan Y, Huang L. In vivo gene delivery to the liver using reconstituted chylomicron remnants as a novel nonviral vector [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(23)∶14547.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Advances of Hepatocyte-Directed Gene Transfer Vectors

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