A microinjected COL7A1-PAC vector restores synthesis of intact procollagen VII in a dystrophic epidermolysis bullosa keratinocyte cell line

Détails

ID Serval
serval:BIB_D66687627F91
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A microinjected COL7A1-PAC vector restores synthesis of intact procollagen VII in a dystrophic epidermolysis bullosa keratinocyte cell line
Périodique
Human Gene Therapy
Auteur(s)
Mecklenbeck  S., Compton  S. H., Mejia  J. E., Cervini  R., Hovnanian  A., Bruckner-Tuderman  L., Barrandon  Y.
ISSN
1043-0342 (Print)
Statut éditorial
Publié
Date de publication
09/2002
Volume
13
Numéro
13
Pages
1655-62
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 1
Résumé
Dystrophic epidermolysis bullosa (DEB) comprises a family of inherited blistering skin disorders for which no corrective therapy currently exists. In the most severe form, the Hallopeau-Siemens subtype (RDEB-HS), the epidermal adhesion protein collagen VII is absent from the skin as a consequence of null mutations in the COL7A1 gene. In order to develop an ex vivo gene therapy approach for DEB, we aimed to restore expression of intact procollagen VII in RDEB-HS keratinocytes. The entire human COL7A1 locus in a P1-derived artificial chromosome (PAC) was transferred to RDEB-HS keratinocytes by microinjection, after which sustained biosynthesis and secretion of procollagen VII was detected for 1 year in vitro. Protein chemical analysis demonstrated that the chain composition, domain structure, N-glycosylation and protein folding of the newly produced procollagen VII were similar, if not identical, to its authentic counterpart, indicating that transgenic procollagen VII was structurally normal. These data demonstrate a "proof of principle" for genomic DNA vectors as a means of restoring collagen VII production in RDEB-HS skin and help develop future gene therapy protocols.
Mots-clé
Chromosomes, Artificial, P1 Bacteriophage/*genetics Collagen Type VII/biosynthesis/*genetics Epidermolysis Bullosa Dystrophica/genetics/metabolism/*therapy *Genetic Vectors/administration & dosage Humans Keratinocytes/metabolism Microinjections Procollagen/biosynthesis/*genetics
Pubmed
Web of science
Création de la notice
28/01/2008 9:41
Dernière modification de la notice
03/03/2018 21:47
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