In vivo delivery of siRNA to key transcipts of fibrogenesis in lipid-like carriers inhibits development liver fibrosis

Introduction: Antifibrotic therapies have to be specific (on target), efficient and free of major side effects. C12–200 lipid-like particles (LPs) consisting of epoxide terminated alkyl chains and secondary amine monomers permit efficient delivery of siRNA, minimizing interference with blood cells and plasma and being devoid of side effects. Intravenous C12–200 LPs allow efficient and safe delivery of small interfering RNAs (siRNAs) to the liver (Akinc et al, Nat Biotechnol 2008). Methods: Optimized siRNAs targeting the fibrogenic genes procollagen α1(I), TGFß1 and Smad2/3 were linked to C12–200 LPs. siGFP (gree…