RNA interference therapy for autosomal dominant osteopetrosis type 2. Towards the preclinical development

Autosomal Dominant Osteopetrosis type 2 (ADO2) is a rare bone disease characterized by dense and brittle bones due to impairment of osteoclast bone resorption. Dominant negative mutations of the CLCN7 gene affect about 70% of ADO2 patients. ADO2 has no cure and our recent work established that it is suitable for gene silencing by a specific small interfering RNA that does not affect the normal mRNA, thus inducing a condition of pseudo-haplosufficiency and rescuing the bone phenotype. We performed a systematic study to test the likelihood that the therapy could progress towards clinical trials, treating Clcn7G213R/WT ADO2 mice with Clcn7G213R-specific siRNA and investigating the bone phenotype by μCT and histomorphometry, and safety, by histopathology and serology.
Source: Bone - Category: Orthopaedics Authors: Tags: Full Length Article Source Type: research