[1]Hong Kong Baptist University, Institute for Advancing Translational Medicine in Bone and Joint Diseases,Hong Kong,China
[2]Hong Kong Baptist University, Kunshan Industrial Technology Research Institute,Hong Kong,China
[3]Chinese University of Hong Kong, Department of Orthopaedics and Traumatology,Hong Kong,China
[4]Chinese University of Hong Kong, Faculty of Medicine,Hong Kong,China
[5]Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone,Hong Kong,China
[6]s Hospital, Department of Orthopaedics and Traumatology,Qingshuihe, Shenzhen,China
[7]Chinese University of Hong Kong, School of Pharmacy,Hong Kong,China
[8]Shanghai Institute of Materia Medica, Chinese Academy of Sciences,Shanghai,China
[9]Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Department of Cognitive Science,Beijing,China
[10]Shenzhen Institute of Advanced Technology, Translational Medicine R&D Center,Qingshuihe, Shenzhen,China
[11]Chinese University of Hong Kong, Department of Diagnostic Radiology and Organ Imaging,Hong Kong,China
[12]Shanghai Jiaotong University, Department of Medicine,Shanghai,China
[13]Nankai University, Institute of Molecular Biology,Tianjin,China
[14]Prince of Wales Hospital Hong Kong, Department of Orthopaedics and Traumatology,Hong Kong,China
[15]Fudan University Shanghai Medical College, State Key Laboratory of Genetic Engineering,Shanghai,China
[16]Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics,Beijing,China
[17]Shenzhen Institute of Advanced Technology, Translational Medicine Research and Development Center,Qingshuihe, Shenzhen,China
Metabolic skeletal disorders associated with impaired bone formation are a major clinical challenge. One approach to treat these defects is to silence bone-formation-inhibitory genes by small interference RNAs (siRNAs) in osteogenic-lineage cells that occupy the niche surrounding the bone-formation surfaces. We developed a targeting system involving dioleoyl trimethylammonium propane (DOTAP)-based cationic liposomes attached to six repetitive sequences of aspartate, serine, serine ((AspSerSer) 6) for delivering siRNAs specifically to bone-formation surfaces. Using this system, we encapsulated an osteogenic siRNA that targets casein kinase-2 interacting protein-1 (encoded by Plekho1, also known as Plekho1). In vivo systemic delivery of Plekho1 siRNA in rats using our system resulted in the selective enrichment of the siRNAs in osteogenic cells and the subsequent depletion of Plekho1. A bioimaging analysis further showed that this approach markedly promoted bone formation, enhanced the bone micro-architecture and increased the bone mass in both healthy and osteoporotic rats. These results indicate (AspSerSer) 6-liposome as a promising targeted delivery system for RNA interference-based bone anabolic therapy. ? 2012 Nature America, Inc. All rights reserved.