自组装 RNA 干扰微海绵用于高效 siRNA 递送。
Self-assembled RNA interference microsponges for efficient siRNA delivery.
机构信息
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
Nat Mater. 2012 Feb 26;11(4):316-22. doi: 10.1038/nmat3253.
The encapsulation and delivery of short interfering RNA (siRNA) has been realized using lipid nanoparticles, cationic complexes, inorganic nanoparticles, RNA nanoparticles and dendrimers. Still, the instability of RNA and the relatively ineffectual encapsulation process of siRNA remain critical issues towards the clinical translation of RNA as a therapeutic. Here we report the synthesis of a delivery vehicle that combines carrier and cargo: RNA interference (RNAi) polymers that self-assemble into nanoscale pleated sheets of hairpin RNA, which in turn form sponge-like microspheres. The RNAi-microsponges consist entirely of cleavable RNA strands, and are processed by the cell's RNA machinery to convert the stable hairpin RNA to siRNA only after cellular uptake, thus inherently providing protection for siRNA during delivery and transport to the cytoplasm. More than half a million copies of siRNA can be delivered to a cell with the uptake of a single RNAi-microsponge. The approach could lead to novel therapeutic routes for siRNA delivery.
使用脂质纳米粒、阳离子复合物、无机纳米粒、RNA 纳米粒和树枝状聚合物已经实现了短干扰 RNA（siRNA）的包裹和递送。然而，RNA 的不稳定性和 siRNA 相对低效的包裹过程仍然是 RNA 作为治疗剂向临床转化的关键问题。在这里，我们报告了一种递送载体的合成，该载体将载体和货物结合在一起：RNA 干扰（RNAi）聚合物，这些聚合物自组装成发夹 RNA 的纳米级褶皱片，进而形成海绵状微球。RNAi 微海绵完全由可切割的 RNA 链组成，并且被细胞的 RNA 机制加工，只有在细胞摄取后，才能将稳定的发夹 RNA 转化为 siRNA，从而在递送到细胞质的过程中为 siRNA 提供内在保护。单个 RNAi 微海绵摄取后，可将超过 50 万份 siRNA 递送到一个细胞中。该方法可能为 siRNA 的递送开辟新的治疗途径。
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