Cancer-specific binary expression system activated in mice by bacteriophage HK022 Integrase.
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.
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Amer
A
Elias
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Itay
I
Spector
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Ilana
I
Sogolovsky-Bard
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Natalia
N
Gritsenko
Department of Oncology 54O5, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark.|Department of Neuroscience and Pharmacology, University of Copenhagen and Department of Clinical Neurophysiology, Rigshospitalet - Glostrup, Entrance 3, 9th floor, Nordre Ringvej 57, 2600 Glostrup, Denmark.
Lene
L
Rask
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Yuli
Y
Mainbakh
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Yael
Y
Zilberstein
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Ezra
E
Yagil
Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Mikhail
M
Kolot
D000818:Animals; D025523:Bacteriophage HK022 / Q000201:enzymology* / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008175:Lung Neoplasms / Q000175:diagnosis*; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic
D011994:Recombinant Proteins; D008156:Luciferases; D019426:Integrases