SIS-101-ADO

SIS-101-ADO is an investigational small interfering RNA (siRNA) therapeutic developed for the treatment of Autosomal Dominant Osteopetrosis Type 2 (ADO2), a rare genetic skeletal disorder. The drug specifically targets and suppresses the expression of the mutant CLCN7 gene, which is implicated in ADO2 pathogenesis. The siRNA sequence is specifically designed against human CLCN7G215R mRNA. By downregulating CLCN7, which is expressed by osteoclasts and other cell types, SIS-101-ADO aims to restore bone mass and quality to near-normal levels. The siRNA payload is delivered using SiSaf’s proprietary Bio-Courier technology—a silicon-stabilized hybrid lipid nanoparticle platform designed for efficient delivery and protection of RNA therapeutics, which enhances stability, loading capacity, and targeted delivery. Preclinical studies have demonstrated significant downregulation of mutant Clcn7 mRNA in bone tissue with rescue of bone phenotype and favorable safety profile. There are currently no approved treatments for ADO2; if successful, SIS-101-ADO would be the first therapy available for this condition[1][2][4][5][6][7][8][9][10].