title: Sustainable correction of junctional epidermolysis bullosa via transposon-mediated nonviral gene transfer.
abstract: Sustainable correction of severe human genetic disorders of self-renewing tissues, such as the blistering skin disease junctional epidermolysis bullosa (JEB), is facilitated by stable genomic integration of therapeutic genes into somatic tissue stem cells. While integrating viral vectors can achieve this, they suffer from logistical and biosafety concerns. To circumvent these limitations, we used the Sleeping Beauty transposable element to integrate the LAMB3 cDNA into genomes of epidermal holoclones from six unrelated JEB patients. These cells regenerate human JEB skin that is normalized at the level of laminin 5 protein expression, hemidesmosome formation and blistering. Transposon-mediated gene delivery therefore affords an opportunity for stable gene delivery in JEB and other human diseases.
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ortiz-Urda
authors.forename: Q
authors.initials: Q
authors.lastname: Lin
authors.forename: S R
authors.initials: SR
authors.lastname: Yant
authors.forename: D
authors.initials: D
authors.lastname: Keene
authors.forename: M A
authors.initials: MA
authors.lastname: Kay
authors.forename: P A
authors.initials: PA
authors.lastname: Khavari
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004251:DNA Transposable Elements; D003896:Desmosomes / Q000648:ultrastructure; D016109:Epidermolysis Bullosa, Junctional / Q000378:metabolism / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D016253:Microscopy, Immunoelectron; D012038:Regeneration; D012867:Skin / Q000648:ultrastructure; D013234:Stem Cells / Q000378:metabolism*; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D004251:DNA Transposable Elements; D000097794:Kalinin