• 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

通过3'末端共轭提高叶酸共轭的完全化学修饰小干扰RNA的细胞积累

Improving the Cellular Accumulation of Folate-Conjugated Fully Chemically Modified siRNAs via 3' Terminal Conjugation.

作者信息

Motosawa Keiichi, Iwano Junko, Harumoto Toshimasa, Yabuuchi Hayato, Hatanaka Kentaro, Koda Yasuo, Kubo Toshiko, Kodaira Hiroshi, Uehara Keiji

机构信息

Research Unit, Research Division, Kyowa Kirin Co., Ltd., 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.

出版信息

ACS Omega. 2025 Jul 25;10(30):32744-32753. doi: 10.1021/acsomega.4c11519. eCollection 2025 Aug 5.

DOI:10.1021/acsomega.4c11519
PMID:40787336
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12332678/
Abstract

Folic acid (FA) conjugation is a validated tumor-specific delivery platform for small molecules. Although targeted delivery using FA-conjugated oligonucleotides, such as microRNA and small interfering RNAs (siRNA), has been reported, the performance of FA-conjugated fully chemically modified siRNAa commonly used siRNA platform in clinical studiesremains unclear. To enhance the cellular accumulation of siRNA and subsequent gene knockdown (KD), we designed various FA-siRNA-based formats and evaluated their performance in folate receptor 1 (FOLR1)-expressing cells. Intracellular accumulation was enhanced by the conjugation of a substituent at the 3' end of the antisense strand in FA-siRNA, which potentially stabilized the siRNA. Our study presents a promising approach for enhancing gene silencing in FOLR1-expressing cells.

摘要

叶酸（FA）偶联是一种经过验证的小分子肿瘤特异性递送平台。尽管已经报道了使用FA偶联的寡核苷酸（如微小RNA和小干扰RNA（siRNA））进行靶向递送，但FA偶联的完全化学修饰的siRNA（临床研究中常用的siRNA平台）的性能仍不清楚。为了增强siRNA的细胞内积累及随后的基因敲低（KD），我们设计了各种基于FA-siRNA的形式，并评估了它们在表达叶酸受体1（FOLR1）的细胞中的性能。通过在FA-siRNA反义链的3'端连接一个取代基增强了细胞内积累，这可能稳定了siRNA。我们的研究提出了一种在表达FOLR1的细胞中增强基因沉默的有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/ac62aa19e736/ao4c11519_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/0a922990cd48/ao4c11519_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/c6584659eca4/ao4c11519_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/1ca68cdfd270/ao4c11519_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/81ae27bc418f/ao4c11519_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/e9508e428428/ao4c11519_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/ac62aa19e736/ao4c11519_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/0a922990cd48/ao4c11519_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/c6584659eca4/ao4c11519_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/1ca68cdfd270/ao4c11519_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/81ae27bc418f/ao4c11519_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/e9508e428428/ao4c11519_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/12332678/ac62aa19e736/ao4c11519_0006.jpg

相似文献

1
Improving the Cellular Accumulation of Folate-Conjugated Fully Chemically Modified siRNAs via 3' Terminal Conjugation.通过3'末端共轭提高叶酸共轭的完全化学修饰小干扰RNA的细胞积累
ACS Omega. 2025 Jul 25;10(30):32744-32753. doi: 10.1021/acsomega.4c11519. eCollection 2025 Aug 5.
2
Prescription of Controlled Substances: Benefits and Risks管制药品的处方：益处与风险
3
-Related Cerebral Folate Transport Deficiency- 相关脑叶酸转运缺陷
4
Conjugation-based genetic manipulation of .基于共轭的……基因操作 （原文句子不完整，翻译可能不太准确，你可补充完整原文以便更准确翻译）
mBio. 2025 Jul 30:e0171425. doi: 10.1128/mbio.01714-25.
5
Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.系统性药理学治疗慢性斑块状银屑病：网络荟萃分析。
Cochrane Database Syst Rev. 2021 Apr 19;4(4):CD011535. doi: 10.1002/14651858.CD011535.pub4.
6
Management of urinary stones by experts in stone disease (ESD 2025).结石病专家对尿路结石的管理（2025年结石病专家共识）
Arch Ital Urol Androl. 2025 Jun 30;97(2):14085. doi: 10.4081/aiua.2025.14085.
7
Systematic Evaluation of Position-Specific Tolerability of Seven Backbone and Ribose Modifications in Fully Chemically Stabilized siRNAs.对完全化学稳定的小干扰RNA中七种主链和核糖修饰的位点特异性耐受性的系统评估
Nucleic Acid Ther. 2025 Jun;35(3):137-149. doi: 10.1089/nat.2024.0077. Epub 2025 May 26.
8
Nucleic Acid Nanocapsules as a New Platform to Deliver Therapeutic Nucleic Acids for Gene Regulation.核酸纳米胶囊作为用于基因调控的治疗性核酸递送新平台。
Acc Chem Res. 2025 Jul 1;58(13):1951-1962. doi: 10.1021/acs.accounts.5c00126. Epub 2025 Jun 9.
9
Survivor, family and professional experiences of psychosocial interventions for sexual abuse and violence: a qualitative evidence synthesis.性虐待和暴力的心理社会干预的幸存者、家庭和专业人员的经验：定性证据综合。
Cochrane Database Syst Rev. 2022 Oct 4;10(10):CD013648. doi: 10.1002/14651858.CD013648.pub2.
10
The educational effects of portfolios on undergraduate student learning: a Best Evidence Medical Education (BEME) systematic review. BEME Guide No. 11.档案袋对本科学生学习的教育效果：最佳证据医学教育（BEME）系统评价。BEME指南第11号。
Med Teach. 2009 Apr;31(4):282-98. doi: 10.1080/01421590902889897.

本文引用的文献

1
Targeted delivery to macrophages and dendritic cells by chemically modified mannose ligand-conjugated siRNA.通过化学修饰的甘露糖配体偶联的 siRNA 靶向递送至巨噬细胞和树突状细胞。
Nucleic Acids Res. 2022 May 20;50(9):4840-4859. doi: 10.1093/nar/gkac308.
2
Enhancement of Gene Knockdown on CD22-Expressing Cells by Chemically Modified Glycan Ligand-siRNA Conjugates.化学修饰聚糖配体-siRNA 缀合物增强 CD22 表达细胞的基因敲低。
ACS Chem Biol. 2022 Feb 18;17(2):292-298. doi: 10.1021/acschembio.1c00652. Epub 2022 Jan 12.
3
Syntheses of Morpholine-Based Nucleotide Analogs for Hepatic siRNA Targeting and Stabilization.
基于吗啉核苷酸类似物的合成用于肝 siRNA 靶向和稳定。
J Med Chem. 2021 May 27;64(10):6838-6855. doi: 10.1021/acs.jmedchem.1c00144. Epub 2021 May 5.
4
Investigating the pharmacodynamic durability of GalNAc-siRNA conjugates.研究 GalNAc-siRNA 缀合物的药效持久性。
Nucleic Acids Res. 2020 Dec 2;48(21):11827-11844. doi: 10.1093/nar/gkaa670.
5
Advances in oligonucleotide drug delivery.寡核苷酸药物递送的进展。
Nat Rev Drug Discov. 2020 Oct;19(10):673-694. doi: 10.1038/s41573-020-0075-7. Epub 2020 Aug 11.
6
Less Is More: Novel Hepatocyte-Targeted siRNA Conjugates for Treatment of Liver-Related Disorders.少即是多：用于治疗肝脏相关疾病的新型肝细胞靶向小干扰RNA缀合物
Mol Ther Nucleic Acids. 2020 Sep 4;21:242-250. doi: 10.1016/j.omtn.2020.05.026. Epub 2020 May 22.
7
Therapeutic siRNA: state of the art.治疗性 siRNA：最新进展。
Signal Transduct Target Ther. 2020 Jun 19;5(1):101. doi: 10.1038/s41392-020-0207-x.
8
Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria.急性间歇性卟啉症的 RNAi 治疗药物 Givosiran 的 3 期临床试验。
N Engl J Med. 2020 Jun 11;382(24):2289-2301. doi: 10.1056/NEJMoa1913147.
9
Generation and validation of structurally defined antibody-siRNA conjugates.生成和验证结构定义的抗体-siRNA 缀合物。
Nucleic Acids Res. 2020 Jun 4;48(10):5281-5293. doi: 10.1093/nar/gkaa286.
10
Exploiting the folate receptor α in oncology.在肿瘤学中利用叶酸受体α。
Nat Rev Clin Oncol. 2020 Jun;17(6):349-359. doi: 10.1038/s41571-020-0339-5. Epub 2020 Mar 9.