Nanobiomedical Center, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Nat Nanotechnol. 2011 Sep 11;6(10):658-67. doi: 10.1038/nnano.2011.105.
RNA nanoparticles have applications in the treatment of cancers and viral infection; however, the instability of RNA nanoparticles has hindered their development for therapeutic applications. The lack of covalent linkage or crosslinking in nanoparticles causes dissociation in vivo. Here we show that the packaging RNA of bacteriophage phi29 DNA packaging motor can be assembled from 3-6 pieces of RNA oligomers without the use of metal salts. Each RNA oligomer contains a functional module that can be a receptor-binding ligand, aptamer, short interfering RNA or ribozyme. When mixed together, they self-assemble into thermodynamically stable tri-star nanoparticles with a three-way junction core. These nanoparticles are resistant to 8 M urea denaturation, are stable in serum and remain intact at extremely low concentrations. The modules remain functional in vitro and in vivo, suggesting that the three-way junction core can be used as a platform for building a variety of multifunctional nanoparticles. We studied 25 different three-way junction motifs in biological RNA and found only one other motif that shares characteristics similar to the three-way junction of phi29 pRNA.
RNA 纳米颗粒在癌症和病毒感染的治疗中有应用；然而，RNA 纳米颗粒的不稳定性阻碍了它们在治疗应用方面的发展。纳米颗粒中没有共价键或交联导致其在体内解离。在这里，我们展示了噬菌体 phi29 DNA 包装马达的包装 RNA 可以由 3-6 个 RNA 寡聚物组装而成，而无需使用金属盐。每个 RNA 寡聚物都包含一个功能模块，可以是受体结合配体、适体、小干扰 RNA 或核酶。当混合在一起时，它们可以自组装成具有三向连接核心的热力学稳定的三星星形纳米颗粒。这些纳米颗粒可以耐受 8 M 尿素变性，在血清中稳定，并且在极低浓度下保持完整。这些模块在体外和体内仍然保持功能，表明三向连接核心可以用作构建各种多功能纳米颗粒的平台。我们研究了生物 RNA 中的 25 个不同的三向连接基序，只发现了另一个与 phi29 pRNA 的三向连接具有相似特征的基序。
