Anti-cancer binary system activated by bacteriophage HK022 integrase

Amer Elias; Natasha Gritsenko; Rena Gorovits; Itay Spector; Gali Prag; Ezra Yagil; Mikhail Kolot

doi:10.18632/oncotarget.25512

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Research Papers:

Anti-cancer binary system activated by bacteriophage HK022 integrase

Amer Elias, Natasha Gritsenko, Rena Gorovits, Itay Spector, Gali Prag, Ezra Yagil and Mikhail Kolot _

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Oncotarget. 2018; 9:27487-27501. https://doi.org/10.18632/oncotarget.25512

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Abstract

Amer Elias1, Natasha Gritsenko1, Rena Gorovits2, Itay Spector1, Gali Prag1, Ezra Yagil1 and Mikhail Kolot1

1Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel

2Institute of Plant Sciences and Genetics in Agriculture, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel

Correspondence to:

Mikhail Kolot, email: [email protected]

Keywords: cancer therapy; site-specific recombination; coliphage HK022 integrase; lung cancer; DTA toxin

Received: November 09, 2017 Accepted: May 14, 2018 Published: June 08, 2018

ABSTRACT

The binary system presented in this work is based on the bacteriophage HK022 integrase recombinase that activates the expression of a silenced Diphtheria toxin gene, both controlled by the cancer specific hTERT promoter. Using a lung cancer mice model, assays of different apoptotic and anti-apoptotic factors have demonstrated that the Integrase based binary system is highly specific towards cancer cells and more efficient compared to the conventional mono system whose toxin is directly expressed under hTERT. In a mice survival test, this binary system demonstrated longer persistence compared to the untreated and the mono treated ones. The reason underlying the advantage of this binary system over the mono system seems to be an overexpression of various hTERT suppressing factors induced by the mono system.

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Research Papers:

Anti-cancer binary system activated by bacteriophage HK022 integrase

Abstract