The genodermatoses: candidate diseases for gene therapy.

Abstract

Tremendous progress has been made in understanding the genetic basis of different forms of genodermatoses, a group of heritable diseases displaying a spectrum of phenotypic manifestations and clinical severity. The information about the underlying mutations in the candidate gene/protein systems has provided the basis for initial development of cutaneous gene therapy, and these heritable conditions appear to serve as appropriate candidate diseases for such efforts. Because of its accessibility and the fact that resident skin cells, such as epidermal keratinocytes and dermal fibroblasts, can be readily propagated in culture, skin serves as an appropriate target tissue for gene therapy. Various strategic considerations, including the use of in vivo or ex vivo approaches, gene replacement versus gene repair, utilization of different delivery systems, etc., require careful prioritization depending on the type of mutations and their pathogenetic consequences at the mRNA and protein levels.