The epidermis as a bioreactor: Topically regulated cutaneous delivery into the circulation

Tongyu Cao, Sophia Y. Tsai, Bert W. O'Malley, Xiao Jing Wang, Dennis R. Roop

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Previous studies have documented that the skin can be used as a bioreactor to produce proteins for systemic release to treat diseases. A gene-switch system has been developed that allows regulated expression of therapeutic genes. To determine whether this system could be used in the skin, we developed a transgenic mouse model in which expression of a therapeutic gene could be topically induced in epidermal keratinocytes. After a single induction, high levels of the therapeutic protein, human growth hormone (hGH), were released from keratinocytes into the circulation. The serum levels of hGH were dependent on the amount of inducer applied, and repeated induction resulted in increased weight gain by transgenic versus control mice. Furthermore, physiological levels of hGH were detected in the serum of nude mice after topical induction of small transgenic skin grafts. These results clearly demonstrate the feasibility of using the gene-switch system to regulate the delivery of therapeutic proteins into the circulation via genetically modified keratinocytes.

Original languageEnglish (US)
Pages (from-to)1075-1080
Number of pages6
JournalHuman gene therapy
Volume13
Issue number9
DOIs
StatePublished - Jul 14 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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