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Titolo:
TRANSGENIC STUDIES WITH A KERATIN PROMOTER-DRIVEN GROWTH-HORMONE TRANSGENE - PROSPECTS FOR GENE-THERAPY
Autore:
WANG XM; ZINKEL S; POLONSKY K; FUCHS E;
Indirizzi:
UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MOL GENET & CELL BIOL,5841 SMARYLAND AVE,ROOM N314 CHICAGO IL 60637 UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MOL GENET & CELL BIOL CHICAGO IL 60637 UNIV CHICAGO,DEPT MED CHICAGO IL 60637
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 1, volume: 94, anno: 1997,
pagine: 219 - 226
SICI:
0027-8424(1997)94:1<219:TSWAKP>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN EPIDERMAL-KERATINOCYTES; STRATIFIED SQUAMOUS EPITHELIA; TRANSCRIPTIONAL REGULATION; SYSTEMIC DELIVERY; FUSION GENES; HEMOPHILIA-B; MICE; EXPRESSION; CELLS; TISSUE;
Keywords:
KERATINOCYTE; SKIN; TRANSGENIC MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
56
Recensione:
Indirizzi per estratti:
Citazione:
X.M. Wang et al., "TRANSGENIC STUDIES WITH A KERATIN PROMOTER-DRIVEN GROWTH-HORMONE TRANSGENE - PROSPECTS FOR GENE-THERAPY", Proceedings of the National Academy of Sciences of the United Statesof America, 94(1), 1997, pp. 219-226

Abstract

Keratinocytes are potentially appealing vehicles for the delivery of secreted gene products because they can be transferred to human skin by the relatively simple procedure of grafting. Adult human keratinocytes can be efficiently propagated in culture with sufficient proliferative capacity to produce enough epidermis to cover the body surface of an average adult, However, the feasibility of delivering secreted proteins through skin grafting rests upon (i) the strength of the promoterin keratinocytes and (ii) the efficiency of protein transport throughthe basement membrane of the stratified epithelium and into the bloodstream, In this paper, we use transgenic technology to demonstrate that the activity of the human keratin 14 promoter remains high in adult skin and that keratinocyte-derived human growth hormone (hGH) can be produced, secreted, and transported to the bloodstream of mice with efficiency that is sufficient to exceed by an order of magnitude the circulating hGH concentration in growing children. Transgenic skin grafts from these adults continue to produce and secrete hGH stably, at approximate to 1/10 physiological levels in the bloodstream of nontransgenic recipient mice. These studies underscore the utility of the keratin 14 promoter for expressing foreign transgenes in keratinocytes and demonstrate that keratinocytes can be used as effective vehicles for transporting factors to the bloodstream and for eliciting metabolic changes, These findings have important implications for considering the keratinocyte as a possible vehicle for gene therapy.

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Documento generato il 05/12/20 alle ore 05:47:45