Allele dependent silencing of collagen type I using small interfering RNAs targeting 3'UTR Indels - a novel therapeutic approach in osteogenesis imperfecta.

ABSTRACT: Osteogenesis imperfecta, also known as "brittle bone disease", is a heterogeneous disorder of connective tissue generally caused by dominant mutations in the genes COL1A1 and COL1A2, encoding the α1 and α2 chains of type I (pro)collagen. Symptomatic patients are usually prescribed bisphosphonates, but this treatment is neither curative nor sufficient. A promising field is gene silencing through RNA interference. In this study small interfering RNAs (siRNAs) were designed to target each allele of 3'UTR insertion/deletion polymorphisms (indels) in COL1A1 (rs3840870) and COL1A2 (rs3917). For both indels, the frequency of heterozygous individuals was determined to be approximately 50% in Swedish cohorts of healthy controls as well as in patients with osteogenesis imperfecta. Cultures of primar

SUBMITTER: Lindahl K 

PROVIDER: S-EPMC3752721 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature