The dynamic, motile and deformative properties of RNA nanoparticles facilitate the third milestone of drug development.
The dynamic, motile and deformative properties of RNA nanoparticles facilitate the third milestone of drug development.
复制标题
RNA纳米颗粒的动态、运动和变形特性促进了药物开发的第三个里程碑。
DOI：
10.1016/j.addr.2022.114316
复制
发表时间：
2022-07
影响因子：
16.1
通讯作者：
中科院分区：
文献类型：
--
作者：
除了mRNA、rRNA和tRNA外，细胞中还含有许多其他非编码RNA，这些非编码RNA在细胞功能的调节中发挥着关键作用。人类基因组测序显示，大多数非蛋白质编码DNA实际上编码非编码rna。RNA的动态特性导致了它的运动和变形行为。这些构象转变，如碱基配对的改变、互补链内的呼吸、二维水平的假结形成，以及三维水平的诱导配合和构象捕获，对它们的生物学功能（包括调节、翻译和催化）都很重要。这种动态的、可移动的和催化的活性使人们相信RNA是生命的起源。我们最近报道了RNA纳米颗粒的变形特性增强了它们通过癌症渗漏血管的渗透，从而导致高效率的肿瘤积聚。这种特殊的变形特性也使RNA纳米颗粒能够通过肾小球，克服过滤尺寸的限制，导致肾脏快速排泄和身体快速清除，从而低毒性或无毒性。RNA纳米颗粒的生物分布可以通过结合靶向癌症的配体进一步改善。除了良好的生物分布外，RNA纳米颗粒还具有其他特性，包括自组装、负电荷、可编程性和多价性；使其成为一种很好的制药材料。RNA纳米颗粒的固有负电荷通过阻止非特异性结合带负电荷的细胞膜和增强疏水药物的溶解度来降低药物的毒性。RNA纳米颗粒的多价特性允许其多功能化，可用于克服耐药性。本文综述了RNA纳米颗粒的这些独特性质，阐述了RNA的动力学、运动性和变形性的机制，并为RNA治疗学成为药物开发的第三个里程碑做了准备。
Besides mRNA, rRNA, and tRNA, cells contain many other noncoding RNA that display critical roles in the regulation of cellular functions. Human genome sequencing revealed that the majority of non-protein-coding DNA actually codes for non-coding RNAs. The dynamic nature of RNA results in its motile and deformative behavior. These conformational transitions such as the change of base-pairing, breathing within complemented strands, and pseudoknot formation at the 2D level as well as the induced-fit and conformational capture at the 3D level are important for their biological functions including regulation, translation, and catalysis. The dynamic, motile and catalytic activity has led to a belief that RNA is the origin of life. We have recently reported that the deformative property of RNA nanoparticles enhances their penetration through the leaky blood vessel of cancers which leads to highly efficient tumor accumulation. This special deformative property also enables RNA nanoparticles to pass the glomerulus, overcoming the filtration size limit, resulting in fast renal excretion and rapid body clearance, thus low or no toxicity. The biodistribution of RNA nanoparticles can be further improved by the incorporation of ligands for cancer targeting. In addition to the favorable biodistribution profiles, RNA nanoparticles possess other properties including self-assembly, negative charge, programmability, and multivalency; making it a great material for pharmaceutical applications. The intrinsic negative charge of RNA nanoparticles decreases the toxicity of drugs by preventing nonspecific binding to the negative charged cell membrane and enhancing the solubility of hydrophobic drugs. The polyvalent property of RNA nanoparticles allows the multi-functionalization which can apply to overcome drug resistance. This review focuses on the summary of these unique properties of RNA nanoparticles, which describes the mechanism of RNA dynamic, motile and deformative properties, and elucidates and prepares to welcome the RNA therapeutics as the third milestone in pharmaceutical drug development.
登录
查看更多内容
预测RNA伪折叠热力学。
影响因子：
14.9
作者：
Cao, Song;Chen, Shi-Jie
通讯作者：
Chen, Shi-Jie
影响因子：
62.1
作者：
Binzel DW;Li X;Burns N;Khan E;Lee WJ;Chen LC;Ellipilli S;Miles W;Ho YS;Guo P
通讯作者：
Guo P
DOI：
10.1016/j.omtn.2021.07.021
发表时间：
2021-09-03
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Binzel DW;Guo S;Yin H;Lee TJ;Liu S;Shu D;Guo P
通讯作者：
Guo P
影响因子：
3.9
作者：
Brierley, Ian;Gilbert, Robert J. C.;Pennell, Simon
通讯作者：
Pennell, Simon
DOI：
10.2217/nnm-2020-0034
发表时间：
2020-05-26
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Chandler, Morgan;Panigaj, Martin;Afonin, Kirill A
通讯作者：
Afonin, Kirill A