SiRNA-mediated selective inhibition of mutant keratin mRNAs responsible for the skin disorder pachyonychia congenita

RNA interference offers a novel approach for treating genetic disorders including the rare monogenic skin disorder pachyonychia congenita (PC). PC is caused by mutations in keratin 6a (K6a), K6b, K16, and K17 genes, including small deletions and single nucleotide changes. Transfection experiments of a fusion gene consisting of K6a and a yellow fluorescent reporter (YFP) resulted in normal keratin filament formation in transfected cells as assayed by fluorescence microscopy. Similar constructs containing a single nucleotide change (N171K) or a three-nucleotide deletion (N171del) showed keratin aggregate formation. Mutant-specific small inhibitory RNAs (siRNAs) effectively targeted these sites. These studies suggest that siRNAs can discriminate single nucleotide mutations and further suggest that "designer siRNAs" may allow effective treatment of a host of genetic disorders including PC

International strategies of NIC firms in Europe

This article reports on a study of the international strategies of South Korean, Taiwanese, Hong Kong, and Singapore firms in advanced industrialized markets. Thirty-four cases of international strategies were cluster analyzed to identify common strategies. Four main strategies were identified together with their attendant firm characteristics and performance. They include: (1) A strategy of differentiation with aggressive growth objectives and a high degree of parent company support; (2) Low cost strategy and broad product coverage; (3) A focus strategy with limited product range and highly decentralized operation; and (4) A conservative strategy concentrating chiefly on manufacturing skills and serving mainly OEM customers. Variation in performance across clusters was not statistically significant