Gene therapy of epidermolysis bullosa

Expert Opinion on Biological Therapy
Johann W Bauer, Martin Laimer

Abstract

Easy access to the organ and identification of underlying mutations in epidermolysis bullosa (EB) facilitated the first cutaneous gene therapy experiments in vitro in the mid-1990s. The leading technology was transduction of the respective cDNA carried by a retroviral vector. Using this approach, the genotypic and phenotypic hallmark features of the recessive forms of junctional EB, which are caused by loss of function of the structural proteins laminin-5 or bullous pemphigoid antigen 2/type XVII collagen of the dermo-epidermal basement membrane zone, have been corrected in vitro and in vivo using xenograft mouse models. Recently, this approach has also been shown to be feasible for the large COL7A1 gene (mutated in dystrophic EB), applying PhiC31 integrase or lentiviral vectors. Neither of these approaches has made it into a successful Phase I study on EB patients. Therefore, alternative approaches to gene correction, including modulation of splicing, are being investigated for gene therapy in EB.

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Citations

Mar 22, 2006·Expert Opinion on Biological Therapy·Stefano FerrariMichele De Luca
Oct 27, 2007·Stem Cells·Bhaskar ThyagarajanJonathan D Chesnut
Jan 13, 2006·The British Journal of Dermatology·M LaimerH Hinter
Aug 9, 2005·Pathologie-biologie·Sylvie Ricard-Blum, Florence Ruggiero
Jan 25, 2011·The Journal of Dermatological Treatment·Amilcar Ezequiel Rizzo, Howard I Maibach
May 16, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·R SchuchtDagmar Wirth

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