Open AccessIdentification and characterization of a novel peptide ligand of Tie2 for targeting gene therapy
Author(s) -
Wu Xianghua,
Li Zonghai,
Yao Ming,
Wang Huamao,
Qu Sumin,
Chen Xianlian,
Li Jinjun,
Sun Ye,
Xu Yuhong,
Gu Jianren
Publication year - 2008
Publication title -
acta biochimica et biophysica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1111/j.1745-7270.2008.00389.x
Subject(s) - biodistribution , cancer research , genetic enhancement , transgene , polyethylenimine , biology , microbiology and biotechnology , chemistry , in vivo , gene , biochemistry , genetics , transfection
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, 125 I‐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.