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Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue.


ABSTRACT: In spite of advances in the molecular diagnosis of recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering disease due to a deficiency of type VII collagen at the basement membrane zone (BMZ) of stratified epithelium, current therapy is limited to supportive palliation. Gene delivery has shown promise in short-term experiments; however, its long-term sustainability through multiple turnover cycles in human tissue has awaited confirmation. To characterize approaches for long-term genetic correction, retroviral vectors were constructed containing long terminal repeat-driven full-length and epitope-tagged COL7A1 cDNA and evaluated for durability of type VII collagen expression and function in RDEB skin tissue regenerated on immune-deficient mice. Type VII collagen expression was maintained for 1 year in vivo, or over 12 epidermal turnover cycles, with no abnormalities in skin morphology or self-renewal. Type VII collagen restoration led to correction of RDEB disease features, including reestablishment of anchoring fibrils at the BMZ. This approach confirms durably corrective and noninjurious gene delivery to long-lived epidermal progenitors and provides the foundation for a human clinical trial of ex vivo gene delivery in RDEB.

SUBMITTER: Siprashvili Z 

PROVIDER: S-EPMC2957245 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue.

Siprashvili Zurab Z   Nguyen Ngon T NT   Bezchinsky Maria Y MY   Marinkovich M Peter MP   Lane Alfred T AT   Khavari Paul A PA  

Human gene therapy 20101001 10


In spite of advances in the molecular diagnosis of recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering disease due to a deficiency of type VII collagen at the basement membrane zone (BMZ) of stratified epithelium, current therapy is limited to supportive palliation. Gene delivery has shown promise in short-term experiments; however, its long-term sustainability through multiple turnover cycles in human tissue has awaited confirmation. To characterize approaches for long-te  ...[more]

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