title: Allele-specific gene silencing in osteogenesis imperfecta.
abstract: OI is caused by mutations in the genes encoding for collagen type I COL1A1 and COL1A2, respectively. The patients suffer from bone fragility, and the severity can range from mild, with fractures in the youth, to lethal forms. Today, there is no effective treatment for the disorder. OI is caused by dominant negative mutations. A tempting approach to treat the disease would be to silence the allele carrying the mutation. This could in theory be done with siRNAs. Today, more than 800 various mutations are reported, and to create siRNA against a specific mutation is difficult. Instead, by developing siRNA against common polymorphic variations, it would be possible to silence the mutation by a standardized method regardless where the mutation is located on the allele. If the concept of allele-specific gene silencing by inhibitory RNA directed towards dominant negative mutations could be proven, this might be a novel approach to gene therapy in OI.
authors.forename: Östen
authors.initials: Ö
authors.lastname: Ljunggren
authors.forename: Katarina
authors.initials: K
authors.lastname: Lindahl
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Rubin
authors.forename: Andreas
authors.initials: A
authors.lastname: Kindmark
mesh_terms: D000483:Alleles; D020868:Gene Silencing / Q000502:physiology*; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods; D013379:Substrate Specificity / Q000235:genetics