Journal
NATURE MEDICINE
Volume 21, Issue 3, Pages 288-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3791
Keywords
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Funding
- Ministry of Science and Technology of China [2013ZX09301307]
- Hong Kong General Research Fund [HKBU479111, HKBU478312, HKBU12102914, HKBU261113]
- Natural Science Foundation Council of China [81272045, 81228013, 21221003]
- Research Grants Council & Natural Science Foundation Council of China [N_HKBU435/12]
- Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University [RC-IRMS/12-13/02, RC-IRMS/13-14/02]
- Hong Kong Baptist University Strategic Development Fund (SDF) [SDF13-1209-P01]
- Hong Kong Research Grants Council (RGC) Early Career Scheme (ECS) [489213]
- Faculty Research Grant of Hong Kong Baptist University [FRG1/13-14/024, FRG2/12-13/027]
- China Academy of Chinese Medical Sciences [Z0252, Z0293]
- Chinese National High-Tech Research and Development Programme [2012AA022501]
- National Key Technologies R&D Programs for New Drugs of China [2012ZX09301003-001-001, 2014ZX09J14106-04C]
- Collaborative Research Programme (CRP)-International Centre for Genetic Engineering and Biotechnology (ICGEB) grant [CRP/CHN13-02]
- Chinese National Natural Science Foundation Project [81261160503]
- National Key Scientific Program of China [2011CB911000]
- National Institutes of Health [GM079359]
- Beijing Natural Science Foundation [7131012]
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Currently, major concerns about the safety and efficacy of RNA interference (RNAi)-based bone anabolic strategies still exist because of the lack of direct osteoblast-specific delivery systems for osteogenic siRNAs. Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteoblasts, and then we developed CH6 aptamer-functionalized lipid nanoparticles (LNPs) encapsulating osteogenic pleckstrin homology domain-containing family O member 1 (Plekho1) siRNA (CH6-LNPs-siRNA). Our results showed that CH6 facilitated in vitro osteoblast-selective uptake of Plekho1 siRNA, mainly via macropinocytosis, and boosted in vivo osteoblast-specific Plekho1 gene silencing, which promoted bone formation, improved bone microarchitecture, increased bone mass and enhanced mechanical properties in both osteopenic and healthy rodents. These results indicate that osteoblast-specific aptamer-functionalized LNPs could act as a new RNAi-based bone anabolic strategy, advancing the targeted delivery selectivity of osteogenic siRNAs from the tissue level to the cellular level.
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