A Sleeping Beauty DNA transposon-based genetic sensor for functional screening of vitamin D3 analogues |
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| Authors: | Nicklas H Staunstrup Nynne Sharma Rasmus O Bak Lars Svensson Thomas K Petersen Lene Aarenstrup Karsten Kristiansen Lars Bolund Jacob Giehm Mikkelsen |
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| Institution: | (1) Department of Human Genetics, University of Aarhus, DK-8000, Aarhus C, Denmark;(2) Department of Disease Pharmacology, LEO Pharma, DK-2750, Ballerup, Denmark;(3) Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230, Odense M, Denmark;(4) Department of Biology, University of Copenhagen, DK-2200, Copenhagen N, Denmark |
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| Abstract: | Background Analogues of vitamin D3 are extensively used in the treatment of various illnesses, such as osteoporosis, inflammatory skin
diseases, and cancer. Functional testing of new vitamin D3 analogues and formulations for improved systemic and topical administration
is supported by sensitive screening methods that allow a comparative evaluation of drug properties. As a new tool in functional
screening of vitamin D3 analogues, we describe a genomically integratable sensor for sensitive drug detection. This system
facilitates assessment of the pharmacokinetic and pharmadynamic properties of vitamin D3 analogues. The tri-cistronic genetic
sensor encodes a drug-sensoring protein, a reporter protein expressed from an activated sensor-responsive promoter, and a
resistance marker. |
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