Synthesis of siRNAs incorporated with cationic peptides R8G7 and R8A7 and the effect of the modifications on siRNA properties

Matsubara Miho; Honda Kenji; Ozaki Koki; Kajino Ryohei; Kakisawa Yuri; Maeda Yusuke; Ueno Yoshihito

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Synthesis of siRNAs incorporated with cationic peptides R8G7 and R8A7 and the effect of the modifications on siRNA properties

机译：掺入阳离子肽R8G7和R8A7的siRNA的合成及其改性对siRNA性能的影响

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Small interfering RNA (siRNA) can be used as an innovative next-generation drug. However, there are several challenges in the therapeutic application of siRNAs, including their low cell membrane permeability. In this study, we designed and synthesized siRNAs, incorporating the cationic peptides R8G7 and R8A7 to improve cell membrane permeability of siRNAs. Thermal denaturation studies revealed that R8G7 and R8A7 modifications increased the thermal stability of the siRNA duplexes. Incorporating these peptides at the 3 '-ends of the siRNA passenger strands increased the stability of the siRNAs in a buffer containing bovine serum. Further, we found that the peptide-siRNA conjugates did not show sufficient RNA interference (RNAi) activity in the absence of the transfection reagent; however, when the transfection reagent was used, the peptide-siRNA conjugates preserved their RNAi activity.

机译：小干扰RNA（siRNA）可用作创新的下一代药物。然而，SIRNA的治疗施用存在若干挑战，包括它们的低细胞膜渗透性。在本研究中，我们设计和合成了SIRNA，其掺入阳离子肽R8G7和R8A7以改善siRNA的细胞膜渗透性。热变性研究表明，R8G7和R8A7的修饰增加了siRNA双链体的热稳定性。在siRNA乘客链的3'后掺入这些肽在含牛血清的缓冲液中增加了siRNA的稳定性。此外，我们发现肽-SiRNA缀合物在没有转染试剂的情况下没有显示出足够的RNA干扰（RNAi）活性; 然而，当使用转染试剂时，肽 - siRNA缀合物保留其RNAi活性。

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《RSC Advances》 |2020年第57期|共10页
作者
Matsubara Miho; Honda Kenji; Ozaki Koki; Kajino Ryohei; Kakisawa Yuri; Maeda Yusuke; Ueno Yoshihito;
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Gifu Univ Fac Appl Biol Sci Course Appl Life Sci 1-1 Yanagido Gifu 5011193 Japan;

Gifu Univ Fac Appl Biol Sci Course Appl Life Sci 1-1 Yanagido Gifu 5011193 Japan;

Gifu Univ Fac Appl Biol Sci Course Appl Life Sci 1-1 Yanagido Gifu 5011193 Japan;

Gifu Univ United Grad Sch Agr Sci 1-1 Yanagido Gifu 5011193 Japan;

Gifu Univ Fac Appl Biol Sci Course Appl Life Sci 1-1 Yanagido Gifu 5011193 Japan;

Gifu Univ Fac Appl Biol Sci Course Appl Life Sci 1-1 Yanagido Gifu 5011193 Japan;

Gifu Univ Fac Appl Biol Sci Course Appl Life Sci 1-1 Yanagido Gifu 5011193 Japan;

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正文语种 eng
中图分类化学;
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1. Synthesis of siRNAs incorporated with cationic peptides R8G7 and R8A7 and the effect of the modifications on siRNA properties [J] . Matsubara Miho, Honda Kenji, Ozaki Koki, RSC Advances . 2020,第57期

机译：掺入阳离子肽R8G7和R8A7的siRNA的合成及其改性对siRNA性能的影响
2. Intracellular siRNA delivery system using polyelectrolyte complex micelles prepared from VEGF siRNA-PEG conjugate and cationic fusogenic peptide [J] . Lee SH, Kim SH, Park TG Biochemical and Biophysical Research Communications . 2007,第2期

机译：使用由VEGF siRNA-PEG共轭物和阳离子融合肽制备的聚电解质复合胶束的细胞内siRNA递送系统
3. Synthesis and in vitro assessment of chemically modified siRNAs targeting BCL2 that contain 2 '-ribose and triazole-linked backbone modifications [J] . Hagen Gordon, Peel Brandon J., Samis John, MedChemComm . 2015,第6期

机译：合成和体外评估靶向BCL2的含2'-核糖和三唑连接的骨架修饰的siRNA
4. Synthesis and Biological Properties of Peptide-siRNA Conjugates [C] . Zhenjun Yang, Xiaofeng Wang, Yang Liu, Chinese international peptide symposium . 2011

机译：肽 - siRNA缀合物的合成和生物学性质
5. Peptide-mediated delivery of bioactive siRNAs for the treatment of oral cancer [D] . Alexander, Angela 2015

机译：肽介导的生物活性siRNA的递送用于口腔癌的治疗
6. Synthesis and Gene Silencing Properties of siRNAs Containing Terminal Amide Linkages [O] . Maria Gaglione, M. Emilia Mercurio, Nicoletta Potenza, -1

机译：含末端酰胺键的siRNA的合成及基因沉默特性
7. Synthesis of siRNAs incorporated with cationic peptides R8G7 and R8A7 and the effect of the modifications on siRNA properties [O] . Miho Matsubara, Kenji Honda, Koki Ozaki, 2020

机译：掺入阳离子肽R8G7和R8A7的siRNA的合成及其改性对siRNA性能的影响

Synthesis of siRNAs incorporated with cationic peptides R8G7 and R8A7 and the effect of the modifications on siRNA properties

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