Gene therapy of epidermolysis bullosa

Expert Opin Biol Ther. 2004 Sep;4(9):1435-43. doi: 10.1517/14712598.4.9.1435.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / physiology
  • Carrier Proteins
  • Cell Adhesion Molecules / deficiency
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology
  • Collagen Type XVII
  • Cytoskeletal Proteins
  • DNA, Complementary / genetics
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Dystonin
  • Epidermolysis Bullosa / classification
  • Epidermolysis Bullosa / genetics
  • Epidermolysis Bullosa / therapy*
  • Genetic Heterogeneity
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use
  • Humans
  • Integrin beta4 / genetics
  • Integrin beta4 / physiology
  • Kalinin
  • Keratin-14
  • Keratinocytes / metabolism
  • Keratinocytes / transplantation
  • Keratins / deficiency
  • Keratins / genetics
  • Keratins / physiology
  • Matrix Metalloproteinases / physiology
  • Mice
  • Mice, Nude
  • Nerve Tissue Proteins
  • Non-Fibrillar Collagens / deficiency
  • Non-Fibrillar Collagens / genetics
  • Non-Fibrillar Collagens / physiology
  • Protease Inhibitors / therapeutic use
  • RNA Splicing
  • RNA, Catalytic / therapeutic use
  • Telomerase / genetics
  • Telomerase / physiology

Substances

  • Autoantigens
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • DST protein, human
  • Dystonin
  • Integrin beta4
  • KRT14 protein, human
  • Keratin-14
  • Krt14 protein, mouse
  • Nerve Tissue Proteins
  • Non-Fibrillar Collagens
  • Protease Inhibitors
  • RNA, Catalytic
  • Keratins
  • Telomerase
  • Matrix Metalloproteinases