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Allele dependent silencing of COL1A2 using small interfering RNAs.
Lindahl, Katarina; Rubin, Carl-Johan; Kindmark, Andreas; Ljunggren, Osten.
  • Lindahl K; Dept. of Medical Sciences, Uppsala University, Uppsala, Sweden.
Int J Med Sci ; 5(6): 361-5, 2008.
Article en En | MEDLINE | ID: mdl-19015742
ABSTRACT
Osteogenesis imperfecta (OI) is generally caused by a dominant mutation in Collagen I, encoded by the genes COL1A1 and COL1A2. To date there is no satisfactory therapy for OI, but inactivation of the mutant allele through small interfering RNAs (siRNA) is a promising approach, as siRNAs targeting each allele of a polymorphism could be used for allele-specific silencing irrespective of the location of the actual mutations. In this study we examined the allele dependent effects of several tiled siRNAs targeting a region surrounding an exonic COL1A2 T/C polymorphism (rs1800222) in heterozygous primary human bone cells. Relative abundances of COL1A2 alleles were determined by cDNA sequencing and overall COL1A2 abundance was analyzed by quantitative PCR. One of the siRNAs decreased overall COL1A2 abundance by 71% of which 75% was due to silencing of the targeted T-allele. In conclusion, allele-preferential silencing of Collagen type I genes may be a future therapeutic approach for OI.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Silenciador del Gen / Colágeno Tipo I / ARN Interferente Pequeño / Alelos Límite: Humans Idioma: En Año: 2008 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Silenciador del Gen / Colágeno Tipo I / ARN Interferente Pequeño / Alelos Límite: Humans Idioma: En Año: 2008 Tipo del documento: Article