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| October 2000, Volume 7, Number 19, Pages 1640-1647 |
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| Acquired diseases |
| Transcriptional targeting of adenoviral gene delivery into migrating wound keratinocytes using FiRE, a growth factor-inducible regulatory element |
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| P Jaakkola1,a, M Ahonen1,2, V-M Kähäri1,2 and M Jalkanen1 |
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1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Finland
2Departments of Medical Biochemistry, and Dermatology, University of Turku, Turku, Finland
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Correspondence to: V-M Kähäri, Turku Centre for Biotechnology, University of Turku, Tykistökatu 6B, FIN-20520 Turku, Finland
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aCurrent address: Wellcome Trust Centre, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK |
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| Abstract |
| Impaired cutaneous wound healing is a common complication in diabetes, ischemia and venous insufficiency of lower extremities, and in long-term treatment with corticosteroids or other immunosuppressive agents. In development of gene therapy for wound repair, expression of therapeutic transgenes should be precisely targeted and controlled. Here, we describe a recombinant adenovirus RAdFiRE-EGFP, in which a growth factor inducible element (FiRE) of the murine syndecan-1 gene controls the expression of enhanced green fluorescent protein (EGFP) reporter gene. Treatment of RAdFiRE-EGFP-transduced murine epidermal keratinocytes in culture with FiRE-activating growth factor markedly enhanced the expression of EGFP. In ex vivo organ culture of wounded murine skin transduced with RAdFiRE-EGFP, the EGFP expression was specifically detected in wound margin keratinocytes, but not in intact skin. Activity of EGFP was first detected 2 days after a single application of RAdFiRE-EGFP and persisted up to 10 days. Similarly, FiRE-driven EGFP expression was detected specifically in epidermal keratinocytes in the edge of incisional wounds in murine skin transduced with RAdFiRE-EGFP. In contrast, adenovirus-mediated lacZ expression driven by CMV promoter was detected scattered in epidermal, dermal and subcutaneous layers in ex vivo and in vivo wounds, as well as in intact skin. These data demonstrate the feasibility of FiRE as a tool for transcriptional targeting of adenovirus-mediated transgene expression to cutaneous wound edge keratinocytes. Gene Therapy (2000) 7, 1640-1647. |
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| Keywords |
| adenovirus; EGF; FiRE; syndecan-1; transcription; wound repair |
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| Received 28 February 2000; accepted 5 July 2000 |
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| October 2000, Volume 7, Number 19, Pages 1640-1647 |
| Table of contents Previous Abstract Next Full text PDF |
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