Short Report
European Journal of Human Genetics (2004) 12, 864–866. doi:10.1038/sj.ejhg.5201230 Published online 7 July 2004
RNAi of COL1A1 in mesenchymal progenitor cells
Sophia Millington-Ward1, Helena P McMahon1, Danny Allen1, Gearóid Tuohy1, Anna-Sophia Kiang1, Arpad Palfi1, Paul F Kenna1, Peter Humphries1 and G Jane Farrar1
1Ocular Genetics Unit, Department of Genetics, Trinity College Dublin, Dublin 2, Ireland
Correspondence: Dr S Millington-Ward, Ocular Genetics Unit, Department of Genetics, Trinity College Dublin, Dublin 2, Ireland. Tel: +353 1 6082482; Fax: +353 1 6083848; E-mail: sophia@maths.tcd.ie
Received 2 December 2003; Revised 16 April 2004; Accepted 22 April 2004; Published online 7 July 2004.
Abstract
Given that mutant COL1A1 is known to cause Osteogenesis Imperfecta (OI), tools to modulate COL1A1 expression are likely to be of significant therapeutic value. In this context, we have evaluated RNA interference (RNAi) as a means to downregulate COL1A1 expression in Cos-7 cells and in human mesenchymal progenitor stem cells (MPCs), the latter cells giving rise to bone and therefore representing a target cell type for collagen-related disorders. In addition, allele-specificity, a key factor to the success of RNAi-based suppression, was explored with a view to developing a mutation-independent RNAi-based therapeutic for OI by targeting an intragenic SNP within transcripts derived from the COL1A1 gene. Preferential suppression of individual polymorphic alleles that differed by a single nucleotide was observed.
Keywords:
RNAi, polymorphism, COL1A1, gene therapy, stem cell, Osteogenesis Imperfecta
