稳定的RNA纳米颗粒作为癌症治疗的潜在新一代药物。

Stable RNA nanoparticles as potential new generation drugs for cancer therapy.

作者信息

Shu Yi, Pi Fengmei, Sharma Ashwani, Rajabi Mehdi, Haque Farzin, Shu Dan, Leggas Markos, Evers B Mark, Guo Peixuan

机构信息

Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA; Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA.

Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Adv Drug Deliv Rev. 2014 Feb;66:74-89. doi: 10.1016/j.addr.2013.11.006. Epub 2013 Nov 22.

Abstract

Human genome sequencing revealed that only ~1.5% of the DNA sequence coded for proteins. More and more evidence has uncovered that a substantial part of the 98.5% so-called "junk" DNAs actually code for noncoding RNAs. Two milestones, chemical drugs and protein drugs, have already appeared in the history of drug development, and it is expected that the third milestone in drug development will be RNA drugs or drugs that target RNA. This review focuses on the development of RNA therapeutics for potential cancer treatment by applying RNA nanotechnology. A therapeutic RNA nanoparticle is unique in that its scaffold, ligand, and therapeutic component can all be composed of RNA. The special physicochemical properties lend to the delivery of siRNA, miRNA, ribozymes, or riboswitches; imaging using fluogenenic RNA; and targeting using RNA aptamers. With recent advances in solving the chemical, enzymatic, and thermodynamic stability issues, RNA nanoparticles have been found to be advantageous for in vivo applications due to their uniform nano-scale size, precise stoichiometry, polyvalent nature, low immunogenicity, low toxicity, and target specificity. In vivo animal studies have revealed that RNA nanoparticles can specifically target tumors with favorable pharmacokinetic and pharmacodynamic parameters without unwanted accumulation in normal organs. This review summarizes the key studies that have led to the detailed understanding of RNA nanoparticle formation as well as chemical and thermodynamic stability issue. The methods for RNA nanoparticle construction, and the current challenges in the clinical application of RNA nanotechnology, such as endosome trapping and production costs, are also discussed.

摘要

人类基因组测序显示,只有约1.5%的DNA序列编码蛋白质。越来越多的证据表明,那98.5%所谓的“垃圾”DNA中有很大一部分实际上编码非编码RNA。化学药物和蛋白质药物这两个里程碑已经出现在药物研发史上,预计药物研发的第三个里程碑将是RNA药物或靶向RNA的药物。本综述聚焦于应用RNA纳米技术开发用于潜在癌症治疗的RNA疗法。治疗性RNA纳米颗粒的独特之处在于其支架、配体和治疗成分都可以由RNA组成。这些特殊的物理化学性质有助于小干扰RNA(siRNA)、微小RNA(miRNA)、核酶或核糖开关的递送;利用荧光RNA进行成像;以及利用RNA适配体进行靶向。随着在解决化学、酶促和热力学稳定性问题方面的最新进展,由于其均匀的纳米级尺寸、精确的化学计量、多价性质、低免疫原性、低毒性和靶向特异性,RNA纳米颗粒已被发现有利于体内应用。体内动物研究表明,RNA纳米颗粒可以特异性靶向肿瘤,具有良好的药代动力学和药效学参数,且不会在正常器官中产生不必要的积累。本综述总结了那些促成对RNA纳米颗粒形成以及化学和热力学稳定性问题有详细了解的关键研究。还讨论了RNA纳米颗粒的构建方法以及RNA纳米技术临床应用中当前面临的挑战,如内体捕获和生产成本等。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索