A novel receptor-targeted gene delivery system for cancer gene therapy

Science in China. Series C, Life Sciences
P TianJ Gu

Abstract

Some growth factor receptors, such as insulin like growth factor I and II receptor (IGF I R, IGF II R) and epidermal growth factor receptor (EGF R), have been proved to be over-expressed in a variety of human cancers derived from different tissue origins. Based on this molecular alteration, a polypeptide conjugate gene delivery system was designed and synthesized. It contains three essential moieties: a ligand oligopeptide (LOP) for receptor recognition, a polycationic polypeptide (PCP) such as protamine (PA) or poly-L-lysine (PL) as a backbone for DNA binding and an endosome-releasing oligopeptide (EROP) such as influenza haemagglutinin oligopeptide (HA20) for endosomolysis. These components are covalently conjugated as LOP-PCP-HA20 or in the form of a mixture of LOP-PCP and HA20-PCP. A 14 amino acid E5 was designed and synthesized as LOP for IGF I R and IGF II R, and a 16 amino acid GE7 as LOP for EGF R. Both E5 and GE7 systems could form stable complex with the plasmid DNA as E5-PCP/ DNA/PCP-HA20 and GE7-PCP/DNA/PCP-HA20. Using bacterial beta-galactosidase gene (pSVbeta-gal) as a reporter, the present system is able to efficiently target exogenous gene to human cancer cells of different tissue types with high efficiency both...Continue Reading

References

Feb 25, 1993·Nucleic Acids Research·P MidouxA C Roche
Feb 1, 1996·Current Opinion in Genetics & Development·J W Harper, S J Elledge

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Citations

Jul 4, 2001·International Journal of Cancer. Journal International Du Cancer·T K LeeI O Ng
Jun 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shahir S RizkAnthony A Kossiakoff
Dec 20, 2011·Bioconjugate Chemistry·Shahir S RizkAnthony A Kossiakoff
Mar 13, 2003·World Journal of Gastroenterology : WJG·Chun-Hong MaXiao-Hong Liang
Mar 27, 2019·ACS Nano·Liangjun ZhaoM G Finn

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