Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery
Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery
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DOI：
10.1038/mt.2011.35
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发表时间：
2011-07-01
影响因子：
12.4
通讯作者：
Li, Qi-Xiang
中科院分区：
文献类型：
--
作者：
Abdelmawla, Sherine;Guo, Songchuan;Li, Qi-Xiang
先前的研究表明，噬菌体phi29 DNA包装马达的包装RNA（pRNA）折叠成紧密结构，构成一种RNA纳米颗粒，其可作为纳米递送系统与功能基团模块化。pRNA纳米颗粒也可通过二分法自组装而不改变折叠特性。本研究证明，通过这种可扩展的二分策略可轻松制备2'-F修饰的pRNA纳米颗粒，其具有全化学合成的特点，并允许多种功能模块化。这些RNA纳米颗粒在化学和代谢上稳定，并在小鼠体内显示出良好的药代动力学（PK）特征（半衰期（T(1/2)）：5 - 10小时，清除率（CI）：
Previous studies have shown that the packaging RNA (pRNA) of bacteriophage phi29 DNA packaging motor folds into a compact structure, constituting a RNA nanoparticle that can be modularized with functional groups as a nanodelivery system. pRNA nanoparticles can also be self-assembled by the bipartite approach without altering folding property. The present study demonstrated that 2'-F-modified pRNA nanoparticles were readily manufactured through this scalable bipartite strategy, featuring total chemical synthesis and permitting diverse functional modularizations. The RNA nanoparticles were chemically and metabolically stable and demonstrated a favorable pharmacokinetic (PK) profile in mice (half-life (T(1/2)): 5-10 hours, clearance (CI):