A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy
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AbstractMetabolic 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.
All Author(s) ListZhang 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
Journal nameNature Medicine
Detailed descriptionTo ORKTS: Updatd this record and deleted duplications (P116520 & P125334) on 25-Feb-2015.
Year2012
Month2
Day1
Volume Number18
Issue Number2
PublisherNature Publishing Group
Pages307 - 314
ISSN1078-8956
eISSN1546-170X
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Medicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Research & Experimental Medicine

Last updated on 2020-30-05 at 00:40