A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin. / Staunstrup, Nicklas Heine; Bak, Rasmus Otkjær; Cai, Yujia; Svensson, Lars; Petersen, Anette Thomas; Rosada, Cecilia; Stenderup, Karin; Bolund, Lars; Mikkelsen, Jacob Giehm.

In: Experimental Dermatology, Vol. 22, No. 3, 22.03.2013, p. 178-83.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{eeaf4a81970a47ffa1bc585a84c92c2f,
title = "A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin",
abstract = "Vitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin. We generate a bipartite, genetic sensor technology that combines efficient lentivirus-directed gene delivery to xenotransplanted human skin with vitamin D3-induced expression of a luciferase reporter gene and live imaging of animals by bioluminescence imaging. Based on the induction of a transcriptional activator consisting of the vitamin D receptor fused to the Gal4 DNA-binding domain, the vitamin D3-responsive sensor facilitates non-invasive and rapid assessment of permeability and functional properties of vitamin D3 analogues. By topical application of a panel of vitamin D3 analogues onto 'sensorized' human skin, the sensor produces a drug-induced readout with a magnitude and persistence that allow a direct comparative analysis of different analogues. This novel genetic tool has great potential as a non-invasive in vivo screening system for further development and refinement of vitamin D3 analogues.",
author = "Staunstrup, {Nicklas Heine} and Bak, {Rasmus Otkj{\ae}r} and Yujia Cai and Lars Svensson and Petersen, {Anette Thomas} and Cecilia Rosada and Karin Stenderup and Lars Bolund and Mikkelsen, {Jacob Giehm}",
note = "{\textcopyright} 2013 John Wiley & Sons A/S.",
year = "2013",
month = mar,
day = "22",
doi = "10.1111/exd.12091",
language = "English",
volume = "22",
pages = "178--83",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin

AU - Staunstrup, Nicklas Heine

AU - Bak, Rasmus Otkjær

AU - Cai, Yujia

AU - Svensson, Lars

AU - Petersen, Anette Thomas

AU - Rosada, Cecilia

AU - Stenderup, Karin

AU - Bolund, Lars

AU - Mikkelsen, Jacob Giehm

N1 - © 2013 John Wiley & Sons A/S.

PY - 2013/3/22

Y1 - 2013/3/22

N2 - Vitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin. We generate a bipartite, genetic sensor technology that combines efficient lentivirus-directed gene delivery to xenotransplanted human skin with vitamin D3-induced expression of a luciferase reporter gene and live imaging of animals by bioluminescence imaging. Based on the induction of a transcriptional activator consisting of the vitamin D receptor fused to the Gal4 DNA-binding domain, the vitamin D3-responsive sensor facilitates non-invasive and rapid assessment of permeability and functional properties of vitamin D3 analogues. By topical application of a panel of vitamin D3 analogues onto 'sensorized' human skin, the sensor produces a drug-induced readout with a magnitude and persistence that allow a direct comparative analysis of different analogues. This novel genetic tool has great potential as a non-invasive in vivo screening system for further development and refinement of vitamin D3 analogues.

AB - Vitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin. We generate a bipartite, genetic sensor technology that combines efficient lentivirus-directed gene delivery to xenotransplanted human skin with vitamin D3-induced expression of a luciferase reporter gene and live imaging of animals by bioluminescence imaging. Based on the induction of a transcriptional activator consisting of the vitamin D receptor fused to the Gal4 DNA-binding domain, the vitamin D3-responsive sensor facilitates non-invasive and rapid assessment of permeability and functional properties of vitamin D3 analogues. By topical application of a panel of vitamin D3 analogues onto 'sensorized' human skin, the sensor produces a drug-induced readout with a magnitude and persistence that allow a direct comparative analysis of different analogues. This novel genetic tool has great potential as a non-invasive in vivo screening system for further development and refinement of vitamin D3 analogues.

U2 - 10.1111/exd.12091

DO - 10.1111/exd.12091

M3 - Journal article

C2 - 23489420

VL - 22

SP - 178

EP - 183

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 3

ER -