A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy
Publication in refereed journal


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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.
著者Zhang G, Guo BS, Wu H, Tang T, Zhang BT, Zheng LZ, He YX, Yang ZJ, Pan XH, Chow H, To K, Li YP, Li DH, Wang XL, Wang YX, Lee K, Hou ZB, Dong N, Li G, Leung K, Hung L, He FC, Zhang LQ, Qin L
期刊名稱Nature Medicine
詳細描述To ORKTS: Updatd this record and deleted duplications (P116520 & P125334) on 25-Feb-2015.
出版年份2012
月份2
日期1
卷號18
期次2
出版社Nature Publishing Group
頁次307 - 314
國際標準期刊號1078-8956
電子國際標準期刊號1546-170X
語言英式英語
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Medicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Research & Experimental Medicine

上次更新時間 2020-12-07 於 02:31