Anti-cancer binary system activated by bacteriophage HK022 integrase

// Amer Elias 1 , Natasha Gritsenko 1 , Rena Gorovits 2 , Itay Spector 1 , Gali Prag 1 , Ezra Yagil 1 and Mikhail Kolot 1 1 Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel 2 Institute 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: kolott@post.tau.ac.il 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.