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

文献类型：期刊论文

作者Zhang, Ge2; Guo, Baosheng2; Wu, Heng2; Tang, Tao2; Zhang, Bao-Ting2,3; Zheng, Lizhen2; He, Yixin2; Yang, Zhijun4; Pan, Xiaohua5; Chow, Heelum6
刊名NATURE MEDICINE
出版日期2012-02
卷号18期号:2页码:307-314
ISSN号1078-8956
DOI10.1038/nm.2617
文献子类Article
英文摘要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.
WOS关键词PARATHYROID-HORMONE ; POSTMENOPAUSAL WOMEN ; OSTEOPOROSIS ; THERAPEUTICS ; ALENDRONATE ; COMBINATION ; DEPOSITION ; FRACTURES ; CULTURES ; DOMAINS
资助项目Chinese National Basic Research Programs[2011CB910602] ; Hong Kong Competitive Earmarked Research Grant[CUHK479111] ; Hong Kong Competitive Earmarked Research Grant[473011] ; Faculty of Medicine of the Chinese University of Hong Kong[2041478] ; Faculty of Medicine of the Chinese University of Hong Kong[2041525] ; Hong Kong Baptist University[31-08-089] ; Chinese National Natural Science Foundation[30830029] ; National Key Technologies Research and Development Program for New Drugs[2009ZX09503-002]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology ; Research & Experimental Medicine
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000300140300048
源URL[http://119.78.100.183/handle/2S10ELR8/278204]  
专题药物制剂研究中心
通讯作者Qin, Ling
作者单位1.Beijing Inst Radiat Med, State Key Lab Prote, Beijing Proteome Res Ctr, Beijing, Peoples R China;
2.Chinese Univ Hong Kong, Musculoskeletal Res Lab, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China;
3.Chinese Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China;
4.Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China;
5.Ji Nan Univ, Dept Orthoped, Hosp Med Coll 2, Shenzhen Peoples Hosp, Shenzhen, Peoples R China;
6.Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China;
7.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 200031, Peoples R China;
8.Chinese Univ Hong Kong, Dept Imaging & Intervent Radiol, Hong Kong, Hong Kong, Peoples R China;
9.Chinese Univ Hong Kong, Lee Hysan Clin Res Lab, Hong Kong, Hong Kong, Peoples R China;
10.Jinan Univ, Biomed Res & Dev Ctr, Guangdong Prov Key Lab Bioengn Med, Natl Engn Res Ctr Genet Med, Guangzhou, Guangdong, Peoples R China;
推荐引用方式
GB/T 7714		 Zhang, Ge,Guo, Baosheng,Wu, Heng,et al. A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy[J]. NATURE MEDICINE,2012,18(2):307-314.
APA Zhang, Ge.,Guo, Baosheng.,Wu, Heng.,Tang, Tao.,Zhang, Bao-Ting.,...&Qin, Ling.(2012).A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy.NATURE MEDICINE,18(2),307-314.
MLA Zhang, Ge,et al."A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy".NATURE MEDICINE 18.2(2012):307-314.

入库方式： OAI收割

来源：上海药物研究所

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