Document Type

Journal Article

Authors

Ge Zhang, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Baosheng Guo, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Heng Wu, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Tao Tang, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Bao-Ting Zhang, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Lizhen Zheng, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Yixin He, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Zhijun Yang, School of Chinese Medicine, Hong Kong Baptist UniversityFollow
Xiaohua Pan, Department of Orthopedics, Second Hospital of Medical, Shenzhen People's Hospital
Heelum Chow, School of Pharmacy, Chinese University of Hong Kong
Kinwah To, School of Pharmacy, Chinese University of Hong Kong
Yaping Li, Center of Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Dahu Li, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Xinluan Wang, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Yixiang Wang, Department of Imaging and Interventional Radiology, Chinese University of Hong Kong
Kwongman Lee, Lee Hysan Clinical Research Laboratory, Chinese University of Hong Kong
Zhibo Hou, Biomedical Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University
Nan Dong, Institute of Molecular Biology, Nan Kai University
Gang Li, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Kwoksui Leung, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Leungkim Hung, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong
Fuchu He, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Lingqiang Zhang, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Ling Qin, Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong

Department/Unit

School of Chinese Medicine

Title

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

Language

English

Abstract

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.

Publication Date

2012

Source Publication Title

Nature Medicine

Volume

18

Issue

2

Start Page

307

End Page

314

Publisher

Nature Publishing Group

DOI

10.1038/nm.2617

Link to Publisher's Edition

http://dx.doi.org/10.1038/nm.2617

ISSN (print)

10788956

ISSN (electronic)

1546170X

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