Long-term Type VII Collagen Restoration to Human Epidermolysis Bullosa Skin Tissue

Overview

Journal Hum Gene Ther

Specialties Genetics
Pharmacology

Date 2010 May 26

PMID 20497034

Citations 32

Authors

Zurab Siprashvili

Ngon T Nguyen

Maria Y Bezchinsky

M Peter Marinkovich

Alfred T Lane

Paul A Khavari

Affiliations

Soon will be listed here.

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.

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