A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy

Ge ZHANG*, Baosheng GUO, Heng Wu, Tao Tang, Bao Ting Zhang, Lizhen Zheng, Yixin He, Zhijun YANG, Xiaohua Pan, Heelum Chow, Kinwah To, Yaping Li, Dahu Li, Xinluan Wang, Yixiang Wang, Kwongman Lee, Zhibo Hou, Nan Dong, Gang Li, Kwoksui LeungLeungkim Hung, Fuchu He, Lingqiang Zhang, Ling Qin

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

332 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)307-314
Number of pages8
JournalNature Medicine
Issue number2
Publication statusPublished - Feb 2012

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)


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