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Keratinocyte gene therapy: inducible promoters and in vivo control of transgene expression
Author(s) -
Itai K.,
Sawamura D.,
Meng X.,
Hashimoto I.
Publication year - 2001
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1046/j.1365-2230.2001.00883.x
Subject(s) - promoter , transgene , genetic enhancement , gene expression , microbiology and biotechnology , enhancer , in vivo , keratinocyte , biology , gene , regulation of gene expression , in vitro , genetics
Modulation of transgene expression by exogenous agents is an optimal goal in gene therapy. Successful keratinocyte gene therapy requires a promoter–enhancer cassette to regulate expression of the therapeutic gene in vivo . In this study, we first transferred plasmids, constructed by introducing inducible promoters fused to the β‐galactosidase gene ( LAC Z ), into keratinocytes in vitro . Metallothionein (MT) and 1,24‐vitamin D 3 (OH) 2 dehydroxylase (VDH) promoters responded to the inducing agents, Cadmium and 1,25‐vitamin D 3 (OH) 2 (VitD 3 ), respectively. The plasmids were then introduced in vivo using a naked DNA method and the inducible promoters were evaluated by measuring β‐gal activity in rat keratinocytes. Zinc induced the transferred MT promoter activity by ≈ 2‐fold or 10‐fold when administered systemically and topically, respectively. In addition, VitD 3 induced the transferred VDH promoter activity ≈ 10‐fold when administered topically. These data are useful for developing inducible promoters for keratinocyte gene therapy.