Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy.
Chao Liang,Baosheng Guo,Heng Wu,Ningsheng Shao,Defang Li,Jin Liu,Lei Dang,Cheng Wang,Hui Li,Shaohua Li,Wing Ki Lau,Yu Cao,Zhijun Yang,Cheng Lu,Xiaojuan He,Doris W.T. Au,Xiaohua Pan,Bao-Ting Zhang,Changwei Lu,Hong Qi Zhang,Kinman Yue,Airong Qian,Peng Shang,Jiake Xu,Lianbo Xiao,Zhaoxiang Bian,Weihong Tan,Zicai Liang,Fuchu He,Lingqiang Zhang,Aiping Lu,Ge Zhang +31 more
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TLDR
The 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.Abstract:
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.read more
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Aptamers as targeted therapeutics: current potential and challenges
Jiehua Zhou,John J. Rossi +1 more
TL;DR: This Review discusses challenges of clinical translation of therapeutic aptamers, highlighting recent clinical developments and technological advances that have revived the impetus for this promising class of therapeutics.
Journal ArticleDOI
Analysis of aptamer discovery and technology
TL;DR: A critical analysis of the first 25 years of aptamer research is provided to provide suggestions for choosing chemical modifications that can lead to enhanced activity or stability, and propose standards for the characterization of aptamers in the scientific literature.
Journal ArticleDOI
Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation
Defang Li,Jin Liu,Baosheng Guo,Chao Liang,Lei Dang,Cheng Lu,Cheng Lu,Xiaojuan He,Xiaojuan He,Hilda Y. S. Cheung,Liang Xu,Changwei Lu,Bing He,Biao Liu,Atik Badshah Shaikh,Fangfei Li,Luyao Wang,Zhijun Yang,Doris W.T. Au,Songlin Peng,Zong-Kang Zhang,Bao-Ting Zhang,Xiaohua Pan,Xiaohua Pan,Airong Qian,Airong Qian,Peng Shang,Peng Shang,Lianbo Xiao,Lianbo Xiao,Baohong Jiang,Chris K C Wong,Jiake Xu,Zhaoxiang Bian,Zicai Liang,De-An Guo,Hailong Zhu,Weihong Tan,Aiping Lu,Ge Zhang +39 more
TL;DR: The results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation, which may be a strategy for treating skeletal disorders involving a reduction in bone formation.
Journal ArticleDOI
Recent Advances in Aptamer Discovery and Applications.
TL;DR: This review provides update on the recent advances in this rapidly progressing field of research with particular emphasis on generation of aptamers and their applications in biosensing, biotechnology and medicine.
Journal ArticleDOI
Recent Advances in SELEX Technology and Aptamer Applications in Biomedicine
Zhenjian Zhuo,Yuanyuan Yu,Maolin Wang,Jie Li,Zong-Kang Zhang,Jin Liu,Xiaohao Wu,Aiping Lu,Ge Zhang,Bao-Ting Zhang +9 more
TL;DR: The limitations and notable advances of aptamer selection are presented, and the different methods used in the kinetic characterization of aptamers are compared, to comprehensively review the current shortage and achievement ofaptamer-related technology.
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