Volume 40, Issue 3 pp. 217-225

Identification and characterization of a novel peptide ligand of Tie2 for targeting gene therapy

Xianghua Wu

Xianghua Wu

Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai 200032, China

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Zonghai Li

Zonghai Li

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

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Ming Yao

Ming Yao

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

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Huamao Wang

Huamao Wang

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

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Sumin Qu

Sumin Qu

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

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Xianlian Chen

Xianlian Chen

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

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Jinjun Li

Jinjun Li

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

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Ye Sun

Ye Sun

School of Pharmacy, Shanghai Jiao-Tong University, Shanghai 200030, China

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Yuhong Xu

Yuhong Xu

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

School of Pharmacy, Shanghai Jiao-Tong University, Shanghai 200030, China

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Jianren Gu

Corresponding Author

Jianren Gu

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China

*Corresponding author: Tel/Fax, 86-21-64177401; E-mail, [email protected]Search for more papers by this author
First published: 19 March 2008
Citations: 3

This work was supported by a grant from the Major State Basic Research Development Program of China (No. 2004CB518802)

Abstract

Tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2 (Tie2) has been considered as a rational target for gene therapy in solid tumors. In order to identify a novel peptide ligand of Tie2 for targeted gene therapy, we screened a phage display peptide library and identified a candidate peptide ligand NSLSNASEFRAPY (designated GA5). Binding assays and Scatchard analysis revealed that GA5 could specifically bind to Tie2 with a dissociation constant of 2.1 × 10−8 M. In addition, we showed that GA5 was internalized into tumor cells highly expressing Tie2. In the biodistribution assay, 125I-GA5 was mainly accumulated in SPC-A1 xenograft tumors that express Tie2. In gene delivery studies, GA5-conjugated polyethylenimine vector could achieve greater transgene transduction than non-targeted vectors both in vitro and in vivo. Tumor growth inhibition was observed in SPC-A1 xenograft-bearing mice that received eight intratumoral injections of GA5-polyethylenimine/p53 complexes in 3 weeks. The difference in tumor volume between the experiment and control groups was significant (P< 0.05). Our results showed that GA5 is a potentially efficient targeting element for cancer gene or moleculartherapy.

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