Identification and characterization of a novel peptide ligand of Tie2 for targeting gene therapy
Xianghua Wu
Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai 200032, China
Search for more papers by this authorZonghai Li
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorMing Yao
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorHuamao Wang
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorSumin Qu
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorXianlian Chen
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorJinjun Li
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorYe Sun
School of Pharmacy, Shanghai Jiao-Tong University, Shanghai 200030, China
Search for more papers by this authorYuhong 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
Search for more papers by this authorCorresponding 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 authorXianghua Wu
Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai 200032, China
Search for more papers by this authorZonghai Li
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorMing Yao
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorHuamao Wang
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorSumin Qu
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorXianlian Chen
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorJinjun Li
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, China
Search for more papers by this authorYe Sun
School of Pharmacy, Shanghai Jiao-Tong University, Shanghai 200030, China
Search for more papers by this authorYuhong 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
Search for more papers by this authorCorresponding 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 authorThis 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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