Impact of laminin 5 beta 3 gene versus protein replacement on gene expression patterns in junctional epidermolysis bullosa

Molecular therapy studies to date have examined only a limited number of co rrective parameters. To assess more global impacts on cellular gene express ion for two major molecular therapeutic approaches, we compared gene versus protein delivery in the human genetic disease junctional epidermolysis bul losa (JEB). Both gene and protein replacement of the laminin 5 beta3 (beta3 ) adhesion molecule restored normal growth and adhesion to poorly viable JE B cells. Gene expression profiling was then performed using cDNA microarray s. The expression of more genes was normalized after beta3 gene transfer th an after protein transfer. As anticipated for beta3 delivery, many of the g enes whose expression was restored to the normal range were those encoding adhesion molecules and hemidesmosome components. Although gene transfer nor malized the expression of a higher percentage of genes than did protein tra nsfer, neither approach fully normalized expression of all genes examined. In addition, both approaches disrupted the expression of some genes, but pr otein transfer altered expression of a larger proportion of the genes studi ed. Our findings suggest that therapeutic gene and protein delivery may exe rt different effects on gene expression and thus may have implications for the development and analysis of molecular therapies for the treatment of ge netic disorders.