RT Journal Article
SR Electronic
T1 An anti-cancer binary system activated by bacteriophage HK022 Integrase
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 147736
DO 10.1101/147736
A1 Amer Elias
A1 Itay Spector
A1 Natasha Gritsenko
A1 Yael Zilberstein
A1 Rena Gorovits
A1 Gali Prag
A1 Mikhail Kolot
YR 2017
UL http://biorxiv.org/content/early/2017/06/12/147736.abstract
AB Cancer gene therapy is a great promising tool for cancer therapeutics due to the specific targeting based on the cancerous gene expression background. Binary systems based on site-specific recombination are one of the most effective potential approaches for cancer gene therapy. In these systems, a cancer specific promoter expresses a site-specific recombinase/integrase that in turn controls the expression of a toxin gene. In the current study, we have developed a new HK022 bacteriophage Integrase (Int) based binary system activating a Diphtheria toxin (DTA) gene expression specifically in cancer cells. We have demonstrated the efficiency, and the high specificity of the system in vitro in cell cultures and in vivo in a lung cancer mouse model. Strikingly, different apoptotic and anti-apoptotic factors demonstrated a remarkable efficacy killing capability of the Int-based binary system compared to the conventional hTERT-DTA mono system in the LLC-Kat lung cancer mice model; we observed that the active hTERT promoter down regulation by the transcription factors Mad-1 is the cornerstone of this phenomenon. The new Int-based binary system offers advantages over already known counterparts and may therefore be developed into a safer and efficient cancer treatment technology.