Genetic reversion of inherited skin disorders.
Human epidermis is a squamous stratified epithelium whose integrity relies on balanced processes of cell attachment, proliferation, and differentiation. In monogenic skin dermatoses, such as mecano-bullous diseases, or DNA repair deficiencies such as the xeroderma pigmentosum (XP), alterations of skin integrity may have devastating consequences as illustrated by the extremely high epidermal cancer proneness of XP patients. The lack of efficient pharmacological treatments, the easy accessibility of skin, and the possibility of long term culture and genetic manipulations ex vivo of epidermal keratinocytes, have encouraged approaches toward gene transfer and skin therapy prospects. We review here some of the human genetic disorders that exhibit major traits in skin, as well as requirements and difficulties inherent to approaches aimed at stable phenotypic correction.
Magnaldo
Thierry
T
Laboratory of Genetic Instability and Cancer, CNRS UPR2169, André Lwoff Institute, 7 rue Guy Môquet, 94 801 Villejuif, France. magnaldo@infobiogen.fr
Sarasin
Alain
A
D004260:DNA Repair; D015870:Gene Expression; D018390:Gene Targeting; D015316:Genetic Therapy; D006801:Humans; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D012879:Skin Physiological Phenomena; D019076:Transgenes; D014983:Xeroderma Pigmentosum / Q000276:immunology / Q000628:therapy