Chemical synthesis of site-specifically 2'-azido-modified RNA and potential applications for bioconjugation and RNA interference.
Chemical synthesis of site-specifically 2'-azido-modified RNA and potential applications for bioconjugation and RNA interference.
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DOI：
10.1002/cbic.201000646
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发表时间：
2011-01-03
期刊：
影响因子：
3.2
通讯作者：
Micura, Ronald
中科院分区：
文献类型：
--
作者：
Aigner, Michaela;Hartl, Markus;Fauster, Katja;Steger, Jessica;Bister, Klaus;Micura, Ronald
近年来最重要的科学发现之一是RNA干扰（RNAi），它是由小干扰RNA （siRNA）和微RNA （miRNA）诱导的转录后基因沉默机制RNAi为siRNA和miRNA作为治疗多种疾病的药物开辟了新的途径化学修饰的siRNA之所以被大量报道，是因为它们具有增强核酸酶抗性、防止免疫激活、减少脱靶效应、改善药代动力学和药效学性质的潜力，这些都对siRNA作为治疗剂的应用具有重要意义另一个重大的挑战是siRNA的传递，因为这些试剂由于它们的大小和负电荷而不能轻易地穿过细胞膜迄今为止，基于RNAi的最有希望的治疗方法涉及化学修饰的siRNA，可以解决上述一些问题。化学siRNA修饰分为四类：主干修饰、核糖修饰、核碱基修饰和末端修饰，其中核糖修饰是最常见的。[2b]结构上的简单改变，如2‑‑och3和2‑‑‑f，可以显著提高siRNA在不同靶基因上的性能，前提是它们以位点特异性的方式定位特别是，2 - k - f修饰具有在引导链（反义链）上被很好地接受的非凡特性，而大多数其他修饰则被乘客链（义链）更好地耐受引导链被纳入关键的功能颗粒，rna诱导沉默复合体（RISC）；因此，对非原生RNA的识别和区分是非常严格的我们假设具有特定2位叠氮基团（2位- n3）的siRNA应该具有增强性能的潜力，因为该官能团小，极性，并且支持具有a型特征的c3位内切核糖pucker [7]
One of the most important scientific discoveries in the recent past concerns RNA interference (RNAi), which is a post-transcriptional gene-silencing mechanism induced by small interfering RNA (siRNA) and micro-RNA (miRNA).[1] RNAi has opened up new avenues in the development of siRNA and miRNA as therapeutic agents for various diseases.[2] The reason for the large number of reports about chemically modified siRNA is their potential to enhance nuclease resistance, to prevent immune activation, to decrease off-target effects, and to improve pharmacokinetic and pharmacodynamic properties, all of which are important for the application of siRNA as therapeutic agents.[3] Another substantial challenge is siRNA delivery, because these reagents cannot easily traverse cell membranes because of their size and negative charge.[4] To date, the most promising therapeutic approach based on RNAi involves chemically modified siRNA that can resolve some of the issues mentioned above.Chemical siRNA modifications belong to four classes—backbone, ribose, nucleobase, and terminal modifications—with ribose modifications being the most common.[2b] Structurally simple alterations, such as 2о-OCH3 and 2о-F, lead to significantly enhanced performance of siRNA with diverse target genes, provided that they are positioned in a site-specific manner.[3] In particular, 2о-F modifications possess the extraordinary property of being very well accepted onto the guide (antisense) strand, while most other modifications are much better tolerated by the passenger (sense) strand.[5] The guide strand is incorporated into the crucial functional particle, the RNA-induced silencing complex (RISC); thus RNA recognition and discrimination from non-native counterparts is very stringent.[6] We postulated that siRNA with specific 2о-azido groups (2о-N3) should have the potential for enhanced performance, because this functional group is small, polar, and supports the C3о-endo ribose pucker [7] that is characteristic for an A-form
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影响因子：
14.9
作者：
Bramsen JB;Pakula MM;Hansen TB;Bus C;Langkjær N;Odadzic D;Smicius R;Wengel SL;Chattopadhyaya J;Engels JW;Herdewijn P;Wengel J;Kjems J
通讯作者：
Kjems J
影响因子：
1.3
作者：
Efimov, V. A.;Aralov, A. V.;Chakhmakhcheva, O. G.
通讯作者：
Chakhmakhcheva, O. G.
DOI：
10.1073/pnas.2233244100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Bratu, DP;Cha, BJ;Tyagi, S
通讯作者：
Tyagi, S
DOI：
10.1073/pnas.1006447107
发表时间：
2010-08-31
影响因子：
11.1
作者：
El-Sagheer, Afaf H.;Brown, Tom
通讯作者：
Brown, Tom
DOI：
10.1073/pnas.0812101106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Hartl, Markus;Nist, Andrea;Bister, Klaus
通讯作者：
Bister, Klaus