Construction of an EGF receptor-mediated histone H10-based gene delivery system.

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. [ABSTRACT FROM AUTHOR]