Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 40, Issue 3, Pages 217-225Publisher
OXFORD UNIV PRESS
DOI: 10.1111/j.1745-7270.2008.00389.x
Keywords
Tie2; gene therapy; phage display; polyethylenimine; p53 gene
Categories
Ask authors/readers for more resources
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 x 10(-8) M. In addition, we showed that GA5 was internalized into tumor cells highly expressing Tie2. In the biodistribution assay, I-125-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available