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中国生物工程杂志

China Biotechnology
China Biotechnology  2011, Vol. 31 Issue (04): 25-30    DOI:
    
Construction of NGR Peptide Genetically Modified Adenovirus Vector Expressing Three Reporter Genes and Its Experimental Study
FENG Fei-xue, ZHAO Jun-li, WANG Dong-yang, LIU Shi-hai, WANG Li-xian, XIA Hai-bin
Laboratory of Gene Therapy, College of Life Sciences, Shaanxi Normal University, Xi’an 710062,China
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Abstract  

NGR (Asn-Gly-Arg) motif exploited by phage display can selectively recognize neovasculature, and can be used for ligand-directed targeted delivery of various drugs and viral vectors to tumors or to other tissues with an angiogenesis process. Therefore,constructed the adenoviral vector Ad5/E1-mCherry/E3-luciferase-2A-eGFP/fiber-NGR which was modified with NGR peptide in the HI loop of the knob and could express three reporter genes. The study of the adenovirus in vitro and in vivo indicated that the three reporter genes could be expressed successfully and the infection efficiency indicated human breast cancer cell line MDA-MB-231 mediated by constructed adenovirus was higher than that mediated by unmodified control adenovirus Ad5CMVeGFP. The construction of the adenoviral vector laid a foundation for the further research on the target of adenoviral vector modified with NGR peptide and the therapy research of adenoviral vector carrying therapeutic genes in tumor animal model.



Key wordsAdenoviral vector      NGR peptide      Caspid genetically modification      Tumor gene therapy     
Received: 08 November 2010      Published: 26 April 2011
ZTFLH:  Q789  
Cite this article:

FENG Fei-xue, ZHAO Jun-li, WANG Dong-yang, LIU Shi-hai, WANG Li-xian, XIA Hai-bin. Construction of NGR Peptide Genetically Modified Adenovirus Vector Expressing Three Reporter Genes and Its Experimental Study. China Biotechnology, 2011, 31(04): 25-30.

URL:

https://manu60.magtech.com.cn/biotech/     OR     https://manu60.magtech.com.cn/biotech/Y2011/V31/I04/25


[1] Rittner K,Schreiber V,Erbs P,et al. Targeting of adenovirus vectors carrying a tumor cell-specific peptide: in vitro and in vivo studies. Cancer Gene Ther,2007,14(5):509-518.

[2] Belousova N,Krendelchtchikova V,Curiel D T,et al. Modulation of adenovirus vector tropism via incorporation of polypeptide ligands into the fiber protein. J Virol,2002,76(17):8621-8631.

[3] Mizuguchi H,Koizumi N,Hosono T,et al. A simplified system for constructing recombinant adenoviral vectors containing heterologous peptides in the HI loop of their fiber knob. Gene Therapy,2001,8(9):730-735.

[4] Pasqualini R,Koivunen E,Kain R,et al. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res,2000,60(3):722-727.

[5] Riemann D,Kehlen A,Langner J. CD13——not just a marker in leukemia typing. Immunol Today,1999,20(2):83-88.

[6] Corti A,Curnis F,Arap W,et al. The neovasculature homing motif NGR: more than meets the eye. Blood,2008,112(7):2628-2635.

[7] Xia H,Anderson B,Mao Q,et al. Recombinant human adenovirus: targeting to the human transferrin receptor improves gene transfer to brain microcapillary endothelium. J Virol,2000,74(23):11359-11366.

[8] Liu S,Mao Q,Zhang W,et al. Genetically modified adenoviral vector with the protein transduction domain of Tat improves gene transfer to CAR-deficient cells. Biosci Rep,2009,29(2):103-109.

[9] Santoro A,Rimassa L,Sobrero A F,et al. Phase II study of NGR-hTNF, a selective vascular targeting agent, in patients with metastatic colorectal cancer after failure of standard therapy. Eur J Cancer,2010,46(15):2746-2752.

[10] Spitaleri A,Mari S,Curnis F,et al. Structural basis for the interaction of isoDGR with the RGD-binding site of αvβ3 integrin. J Biol Chem,2008,283(28):19757-19768.

[11] Jullienne B,Vigant F,Muth E,et al. Efficient delivery of angiostatin K1-5 into tumors following insertion of an NGR peptide into adenovirus capsid. Gene Ther,2009,16(12):1405-1415.

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