• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

新型 RNA 干扰治疗药物的疗效。

Efficacy of a novel class of RNA interference therapeutic agents.

机构信息

BONAC Corporation, BIO Factory 4F, Aikawa, Kurume, Fukuoka, Japan.

出版信息

PLoS One. 2012;7(8):e42655. doi: 10.1371/journal.pone.0042655. Epub 2012 Aug 15.

DOI:10.1371/journal.pone.0042655
PMID:22916145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3419724/
Abstract

RNA interference (RNAi) is being widely used in functional gene research and is an important tool for drug discovery. However, canonical double-stranded short interfering RNAs are unstable and induce undesirable adverse effects, and thus there is no currently RNAi-based therapy in the clinic. We have developed a novel class of RNAi agents, and evaluated their effectiveness in vitro and in mouse models of acute lung injury (ALI) and pulmonary fibrosis. The novel class of RNAi agents (nkRNA®, PnkRNA™) were synthesized on solid phase as single-stranded RNAs that, following synthesis, self-anneal into a unique helical structure containing a central stem and two loops. They are resistant to degradation and suppress their target genes. nkRNA and PnkRNA directed against TGF-β1mRNA ameliorate outcomes and induce no off-target effects in three animal models of lung disease. The results of this study support the pathological relevance of TGF-β1 in lung diseases, and suggest the potential usefulness of these novel RNAi agents for therapeutic application.

摘要

RNA 干扰 (RNAi) 被广泛应用于功能基因研究，是药物发现的重要工具。然而，经典的双链短干扰 RNA 不稳定，并引起不良的不良反应，因此目前临床上尚无基于 RNAi 的治疗方法。我们开发了一类新型的 RNAi 试剂，并在急性肺损伤 (ALI) 和肺纤维化的小鼠模型中评估了它们的效果。新型 RNAi 试剂 (nkRNA®, PnkRNA™) 在固相上作为单链 RNA 合成，合成后，自行退火成一种独特的螺旋结构，包含一个中心茎和两个环。它们具有抗降解性，并抑制其靶基因。nkRNA 和 PnkRNA 针对 TGF-β1mRNA 的表达，可改善三种肺部疾病动物模型的预后，且不会产生脱靶效应。本研究的结果支持 TGF-β1 在肺部疾病中的病理相关性，并提示这些新型 RNAi 试剂在治疗应用中的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/3197bc957003/pone.0042655.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/f228fee84df5/pone.0042655.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/c7ff7decb4a6/pone.0042655.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/f712f8fdae99/pone.0042655.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/cf335526f295/pone.0042655.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/0cd15d71289b/pone.0042655.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/63e27f59a7e9/pone.0042655.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/5ef309e92f80/pone.0042655.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/ce10ed64e2df/pone.0042655.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/81867d80332b/pone.0042655.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/3197bc957003/pone.0042655.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/f228fee84df5/pone.0042655.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/c7ff7decb4a6/pone.0042655.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/f712f8fdae99/pone.0042655.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/cf335526f295/pone.0042655.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/0cd15d71289b/pone.0042655.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/63e27f59a7e9/pone.0042655.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/5ef309e92f80/pone.0042655.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/ce10ed64e2df/pone.0042655.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/81867d80332b/pone.0042655.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a87/3419724/3197bc957003/pone.0042655.g010.jpg

相似文献

1
Efficacy of a novel class of RNA interference therapeutic agents.新型 RNA 干扰治疗药物的疗效。
PLoS One. 2012;7(8):e42655. doi: 10.1371/journal.pone.0042655. Epub 2012 Aug 15.
2
Development and preclinical efficacy of novel transforming growth factor-β1 short interfering RNAs for pulmonary fibrosis.新型转化生长因子-β1 短发夹 RNA 治疗肺纤维化的研发及临床前疗效。
Am J Respir Cell Mol Biol. 2012 Mar;46(3):397-406. doi: 10.1165/rcmb.2011-0158OC. Epub 2011 Oct 27.
3
Small interfering RNAs (siRNAs) targeting TGF-beta1 mRNA suppress asbestos-induced expression of TGF-beta1 and CTGF in fibroblasts.靶向转化生长因子β1（TGF-β1）信使核糖核酸（mRNA）的小分子干扰核糖核酸（siRNAs）可抑制石棉诱导的成纤维细胞中TGF-β1和结缔组织生长因子（CTGF）的表达。
J Environ Pathol Toxicol Oncol. 2009;28(2):109-19. doi: 10.1615/jenvironpatholtoxicoloncol.v28.i2.30.
4
Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice.Lats2 低表达骨髓间充质干细胞改善 LPS 诱导的小鼠急性肺损伤。
Mediators Inflamm. 2019 Oct 21;2019:4851431. doi: 10.1155/2019/4851431. eCollection 2019.
5
Functional peptide nanocarriers for delivery of novel anti-RelA RNA interference agents as a topical treatment of atopic dermatitis.用于递送新型抗RelA RNA干扰剂的功能性肽纳米载体作为特应性皮炎的局部治疗方法
Int J Pharm. 2015 Jul 15;489(1-2):261-7. doi: 10.1016/j.ijpharm.2015.05.003. Epub 2015 May 5.
6
Effects of RNA interference-induced Smad3 gene silencing on pulmonary fibrosis caused by paraquat in mice.RNA 干扰诱导 Smad3 基因沉默对百草枯致小鼠肺纤维化的影响。
Exp Biol Med (Maywood). 2012 May;237(5):548-55. doi: 10.1258/ebm.2011.011280. Epub 2012 May 10.
7
Development of small RNA delivery systems for lung cancer therapy.用于肺癌治疗的小RNA递送系统的开发。
Int J Mol Sci. 2015 Mar 6;16(3):5254-70. doi: 10.3390/ijms16035254.
8
Keratinocyte growth factor expression is suppressed in early acute lung injury/acute respiratory distress syndrome by smad and c-Abl pathways.在早期急性肺损伤/急性呼吸窘迫综合征中，角质形成细胞生长因子的表达通过Smad和c-Abl信号通路受到抑制。
Crit Care Med. 2009 May;37(5):1678-84. doi: 10.1097/CCM.0b013e31819fc81a.
9
Prodigiosin Alleviates Pulmonary Fibrosis Through Inhibiting miRNA-410 and TGF-β1/ADAMTS-1 Signaling Pathway.灵菌红素通过抑制miRNA-410和TGF-β1/ADAMTS-1信号通路减轻肺纤维化。
Cell Physiol Biochem. 2018;49(2):501-511. doi: 10.1159/000492989. Epub 2018 Aug 29.
10
Effect of pravastatin on bleomycin-induced acute lung injury and pulmonary fibrosis.普伐他汀对博来霉素诱导的急性肺损伤和肺纤维化的影响。
Clin Exp Pharmacol Physiol. 2010 Nov;37(11):1055-63. doi: 10.1111/j.1440-1681.2010.05431.x.

引用本文的文献

1
Topical Application of RNAi Therapy Using Surface-Modified Liposomes for Treating Retinal-Vein Occlusion.使用表面修饰脂质体的RNAi疗法局部应用于治疗视网膜静脉阻塞
Molecules. 2025 Jun 17;30(12):2622. doi: 10.3390/molecules30122622.
2
Multifunctional molecular hybrid for targeted colorectal cancer cells: Integrating doxorubicin, AS1411 aptamer, and T9/U4 ASO.用于靶向结肠直肠癌细胞的多功能分子杂化物：整合阿霉素、AS1411适配体和T9/U4反义寡核苷酸。
PLoS One. 2025 Feb 13;20(2):e0317559. doi: 10.1371/journal.pone.0317559. eCollection 2025.
3
RNAi therapeutic strategies for acute respiratory distress syndrome.

本文引用的文献

1
Silencing disease genes in the laboratory and the clinic.在实验室和临床中沉默疾病基因。
J Pathol. 2012 Jan;226(2):365-79. doi: 10.1002/path.2993. Epub 2011 Nov 9.
2
Development and preclinical efficacy of novel transforming growth factor-β1 short interfering RNAs for pulmonary fibrosis.新型转化生长因子-β1 短发夹 RNA 治疗肺纤维化的研发及临床前疗效。
Am J Respir Cell Mol Biol. 2012 Mar;46(3):397-406. doi: 10.1165/rcmb.2011-0158OC. Epub 2011 Oct 27.
3
RNA interference in the clinic: challenges and future directions.临床中的 RNA 干扰：挑战与未来方向。
急性呼吸窘迫综合征的 RNAi 治疗策略。
Transl Res. 2019 Dec;214:30-49. doi: 10.1016/j.trsl.2019.07.011. Epub 2019 Jul 27.
4
(Pro)renin receptor: Involvement in diabetic retinopathy and development of molecular targeted therapy.(Pro) 肾素受体：与糖尿病视网膜病变的发生及其分子靶向治疗的发展有关。
J Diabetes Investig. 2019 Jan;10(1):6-17. doi: 10.1111/jdi.12842. Epub 2018 May 13.
5
Periostin in vitreoretinal diseases.骨膜蛋白与玻璃体视网膜疾病
Cell Mol Life Sci. 2017 Dec;74(23):4329-4337. doi: 10.1007/s00018-017-2651-5. Epub 2017 Sep 14.
6
A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation.一种靶向（前）肾素受体的新型单链RNA干扰治疗剂可抑制眼部炎症。
Mol Ther Nucleic Acids. 2017 Jun 16;7:116-126. doi: 10.1016/j.omtn.2017.01.001. Epub 2017 Jan 12.
7
Aerosol Delivery of siRNA to the Lungs. Part 2: Nanocarrier-based Delivery Systems.小干扰RNA（siRNA）肺部气溶胶递送。第2部分：基于纳米载体的递送系统。
Kona. 2017;34:44-69. doi: 10.14356/kona.2017005. Epub 2016 Apr 30.
8
Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization.新型靶向骨膜蛋白的单链RNA干扰剂对视网膜新生血管化眼的治疗作用
Mol Ther Nucleic Acids. 2017 Mar 17;6:279-289. doi: 10.1016/j.omtn.2017.01.004. Epub 2017 Feb 9.
9
Novel form of miR-29b suppresses bleomycin-induced pulmonary fibrosis.新型miR-29b形式可抑制博来霉素诱导的肺纤维化。
PLoS One. 2017 Feb 24;12(2):e0171957. doi: 10.1371/journal.pone.0171957. eCollection 2017.
10
MicroRNA-29b Overexpression Decreases Extracellular Matrix mRNA and Protein Production in Human Corneal Endothelial Cells.微小RNA-29b过表达降低人角膜内皮细胞中细胞外基质的mRNA和蛋白质生成量。
Cornea. 2016 Nov;35(11):1466-1470. doi: 10.1097/ICO.0000000000000954.
Nat Rev Cancer. 2011 Jan;11(1):59-67. doi: 10.1038/nrc2966. Epub 2010 Dec 16.
4
The acute respiratory distress syndrome: pathogenesis and treatment.急性呼吸窘迫综合征：发病机制与治疗。
Annu Rev Pathol. 2011;6:147-63. doi: 10.1146/annurev-pathol-011110-130158.
5
RNAi and small interfering RNAs in human disease therapeutic applications.RNAi 和小干扰 RNA 在人类疾病治疗应用中的作用。
Trends Biotechnol. 2010 Nov;28(11):570-9. doi: 10.1016/j.tibtech.2010.07.009. Epub 2010 Sep 15.
6
Chemical modification of siRNA.小干扰RNA的化学修饰
Curr Opin Mol Ther. 2010 Apr;12(2):158-67.
7
RNAi nanoparticles in the service of personalized medicine.用于个性化医疗的RNA干扰纳米颗粒。
Nanomedicine (Lond). 2009 Dec;4(8):853-5. doi: 10.2217/nnm.09.74.
8
Direct effects of protein S in ameliorating acute lung injury.直接影响蛋白质 S 在改善急性肺损伤。
J Thromb Haemost. 2009 Dec;7(12):2053-63. doi: 10.1111/j.1538-7836.2009.03642.x. Epub 2009 Oct 8.
9
Synthetic nanocircular RNA for controlling of gene expression.用于控制基因表达的合成纳米环状RNA。
Nucleic Acids Symp Ser (Oxf). 2009(53):65-6. doi: 10.1093/nass/nrp033.
10
Pulmonary fibrosis: pathogenesis, etiology and regulation.肺纤维化：发病机制、病因及调控
Mucosal Immunol. 2009 Mar;2(2):103-21. doi: 10.1038/mi.2008.85. Epub 2009 Jan 7.