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Nature Medicine:能够特异性靶标大鼠和人类成骨细胞的适体CH6

摘要 : 香港浸会大学和军事医学科学院的科学家们通过Cell-SELEX筛选,找到了能够特异性靶标大鼠和人类成骨细胞的适体CH6。

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骨髓基质干细胞的自我更新能力和成骨分化能力会随着年龄增长不断下降,这是导致骨质疏松的重要原因。近年来,研究者们开始尝试通过RNA干扰(RNAi)促进骨骼形成,进而对骨质疏松进行治疗。不过人们对这种策略的安全性和有效性还存有比较大的顾虑,这主要是因为缺乏成骨细胞特异性的siRNA直接递送系统。

香港浸会大学和军事医学科学院的科学家们通过Cell-SELEX筛选,找到了能够特异性靶标大鼠和人类成骨细胞的适体CH6。他们将CH6适体与功能化的脂质纳米颗粒(LNP)结合起来,封装能够促进成骨的Plekho1 siRNA(即CH6-LNPs-siRNA)。这一成果发表在2月9日的Nature Medicine杂志上。

研究人员发现,CH6能在体外实验中,帮助成骨细胞通过巨胞饮选择性摄取Plekho1 siRNA。在骨质疏松和健康的鼠类中,CH6能加强成骨细胞特异性的Plekho1基因沉默,促进骨骼形成,改善骨微结构,增加骨量和增强骨骼机械性能。这项研究向人们展示,适体-功能化LNP可以更好的递送siRNA,并由此促进骨骼形成。

原文链接:Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference–based bone anabolic strategy

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-selecive 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.

来源: Nature Medicine 浏览次数:90

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