RNAi of COL1A1 in mesenchymal progenitor cells.
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.
Millington-Ward
Sophia
S
Ocular Genetics Unit, Department of Genetics, Trinity College Dublin, Dublin 2, Ireland. sophia@maths.tcd.ie
McMahon
Helena P
HP
Allen
Danny
D
Tuohy
Gearóid
G
Kiang
Anna-Sophia
AS
Palfi
Arpad
A
Kenna
Paul F
PF
Humphries
Peter
P
Farrar
G Jane
GJ
D000483:Alleles; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D015536:Down-Regulation; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D034741:RNA, Small Interfering