Cancer-specific binary expression system activated in mice by bacteriophage HK022 Integrase

噬菌体HK022整合酶在小鼠中激活癌症特异性二元表达系统

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作者:Amer Elias, Itay Spector, Ilana Sogolovsky-Bard, Natalia Gritsenko, Lene Rask, Yuli Mainbakh, Yael Zilberstein, Ezra Yagil, Mikhail Kolot

Abstract

Binary systems based on site-specific recombination have been used for tumor specific transcription targeting of suicide genes in animal models. In these binary systems a site specific recombinase or integrase that is expressed from a tumor specific promoter drives tumor specific expression of a cytotoxic gene. In the present study we developed a new cancer specific binary expression system activated by the Integrase (Int) of the lambdoid phage HK022. We demonstrate the validity of this system by the specific expression of a luciferase (luc) reporter in human embryonic kidney 293T (HEK293T) cells and in a lung cancer mouse model. Due to the absence viral vectors and of cytotoxicity the Int based binary system offers advantages over previously described counterparts and may therefore be developed into a safer cancer cell killing system.

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