Published in:
01-08-2003 | Original Paper
Construction of an EGF receptor-mediated histone H10-based gene delivery system
Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2003
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Purpose
To construct an EGF receptor (EGF-R)-mediated histone H10-based gene delivery system for gene therapy.
Methods
A recombinant DNA containing histone H10, EGF-R ligand, and endosomalytic domains was constructed in a prokaryotic vector and expressed in E. coli. Expression of the β-galactosidase (β-gal) gene in the tumor cells and tissues was observed after transduction of the β-gal gene packaged by purified fusion proteins in vitro and in vivo.
Results
As an extension of the research on previously reported chemically synthetic composite polypeptide gene delivery systems, this genetically engineered polypeptide has proved to be capable of targeting the β-galactosidase (β-gal) gene into EGF-R-positive cancer cells both in vitro and in vivo. We also studied the time course of β-gal gene expression in tumor tissues delivered in vivo by this polypeptide vector. At 24 h after administration, expression of the β-galactosidase gene in tumor reached peak levels. The dosage optimization of administered polyplex was also investigated. The optimal dose of polyplex per mouse was 1 μg DNA packaged by 3 μg of composite polypeptide.
Conclusions
The genetically engineered polypeptide based on histone H10 is a promising gene delivery system targeting EGF-R.