• 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

腺病毒与脂质体复合物之间核后递送事件的定量及基于机制的研究。

Quantitative and mechanism-based investigation of post-nuclear delivery events between adenovirus and lipoplex.

作者信息

Hama Susumu, Akita Hidetaka, Iida Shinya, Mizuguchi Hiroyuki, Harashima Hideyoshi

机构信息

Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.

出版信息

Nucleic Acids Res. 2007;35(5):1533-43. doi: 10.1093/nar/gkl1165. Epub 2007 Feb 7.

DOI:10.1093/nar/gkl1165
PMID:17287293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1865055/
Abstract

Quantitative and mechanism-based information on differences in transfection efficiency between viral and non-viral vectors would be highly useful for improving the effectiveness of non-viral vectors. A previous quantitative comparison of intracellular trafficking between adenovirus and LipofectAMINE PLUS (LFN) revealed that the three orders of magnitude lower transfection efficiency of LFN was dominantly rate limited by the post-nuclear delivery process. In the present study, the contribution of transcription and translation processes to the overall differences in the transgene expression efficiency of nucleus-delivered DNA was independently evaluated by quantifying mRNA. As a result, transcription efficiency (E(transcript)) of LFN, denoted as transgene expression divided by the amount of nuclear pDNA was about 16 times less than that for adenovirus. Furthermore, translation efficiency (E(translate)), denoted as transfection activity divided by mRNA expression was approximately 460 times less in LFN. Imaging of the decondensed form of DNA by in situ hybridization revealed that poor decondensation efficiency of LFN is involved in the inferior E(transcript). Moreover, the inferior translation efficiency (E(translate)) of LFN was mainly due to electrostatic interactions between LFN and mRNA. Collectively, an improvement in nuclear decondensation and the diminution of the interaction between vector and mRNA is essential for the development of new generations of non-viral vectors.

摘要

关于病毒载体和非病毒载体转染效率差异的定量及基于机制的信息，对于提高非病毒载体的有效性将非常有用。先前对腺病毒和脂质体转染试剂（LFN）之间细胞内运输的定量比较显示，LFN转染效率低三个数量级主要受核后递送过程的速率限制。在本研究中，通过定量mRNA独立评估了转录和翻译过程对核递送DNA转基因表达效率总体差异的贡献。结果，LFN的转录效率（E（转录本）），即转基因表达除以核内质粒DNA的量，比腺病毒低约16倍。此外，LFN的翻译效率（E（翻译）），即转染活性除以mRNA表达，约低460倍。通过原位杂交对解聚形式的DNA进行成像显示，LFN的解聚效率低下与E（转录本）较差有关。此外，LFN较差的翻译效率（E（翻译））主要是由于LFN与mRNA之间的静电相互作用。总体而言，改善核解聚以及减少载体与mRNA之间的相互作用对于新一代非病毒载体的开发至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/c82db74f60cc/gkl1165f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/ecfe0b02b37d/gkl1165f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/1c8aa32a44a3/gkl1165f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/0840597e3a05/gkl1165f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/22b00c1e8217/gkl1165f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/6bd3b5f5d996/gkl1165f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/c82db74f60cc/gkl1165f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/ecfe0b02b37d/gkl1165f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/1c8aa32a44a3/gkl1165f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/0840597e3a05/gkl1165f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/22b00c1e8217/gkl1165f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/6bd3b5f5d996/gkl1165f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b0/1865055/c82db74f60cc/gkl1165f6.jpg

相似文献

1
Quantitative and mechanism-based investigation of post-nuclear delivery events between adenovirus and lipoplex.腺病毒与脂质体复合物之间核后递送事件的定量及基于机制的研究。
Nucleic Acids Res. 2007;35(5):1533-43. doi: 10.1093/nar/gkl1165. Epub 2007 Feb 7.
2
Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems.腺病毒和脂质体系统之间细胞内运输和核转录的定量比较。
Mol Ther. 2006 Apr;13(4):786-94. doi: 10.1016/j.ymthe.2005.10.007. Epub 2005 Dec 20.
3
Cell cycle dependent transcription, a determinant factor of heterogeneity in cationic lipid-mediated transgene expression.细胞周期依赖性转录，阳离子脂质介导的转基因表达异质性的一个决定性因素。
J Gene Med. 2007 Mar;9(3):197-207. doi: 10.1002/jgm.1010.
4
Intranuclear fluorescence resonance energy transfer analysis of plasmid DNA decondensation from nonviral gene carriers.非病毒基因载体中质粒DNA解聚的细胞核内荧光共振能量转移分析
J Gene Med. 2009 Jul;11(7):615-23. doi: 10.1002/jgm.1338.
5
Post-nuclear gene delivery events for transgene expression by biocleavable polyrotaxanes.通过生物可裂解聚轮烷实现转基因表达的核后基因传递事件。
Biomaterials. 2012 May;33(15):3952-8. doi: 10.1016/j.biomaterials.2012.01.049. Epub 2012 Mar 3.
6
Quantitative comparison of polyethylenimine formulations and adenoviral vectors in terms of intracellular gene delivery processes.聚乙烯亚胺制剂与腺病毒载体在细胞内基因递送过程方面的定量比较。
Gene Ther. 2005 Jul;12(13):1023-32. doi: 10.1038/sj.gt.3302495.
7
Dual imaging of mRNA and protein production: an investigation of the mechanism of heterogeneity in cationic lipid-mediated transgene expression.双重成像 mRNA 和蛋白质的产生：阳离子脂质体介导的转基因表达异质性机制的研究。
Int J Pharm. 2011 Aug 30;415(1-2):218-20. doi: 10.1016/j.ijpharm.2011.05.051. Epub 2011 May 27.
8
Envelope-type lipid nanoparticles incorporating a short PEG-lipid conjugate for improved control of intracellular trafficking and transgene transcription.包封型脂质纳米颗粒，其包含短链聚乙二醇脂质共轭物以改善对细胞内运输和转基因转录的控制。
Biomaterials. 2009 Sep;30(27):4806-14. doi: 10.1016/j.biomaterials.2009.05.036. Epub 2009 Jun 10.
9
Non-linear pharmacodynamics in the transfection efficiency of a non-viral gene delivery system.非病毒基因递送系统转染效率中的非线性药效学
Int J Pharm. 2008 Nov 3;363(1-2):192-8. doi: 10.1016/j.ijpharm.2008.07.020. Epub 2008 Jul 30.
10
Elucidating the pre- and post-nuclear intracellular processing of 1,4-dihydropyridine based gene delivery carriers.阐明基于 1,4-二氢吡啶的基因传递载体的核内预处理和后处理。
J Control Release. 2012 Aug 20;162(1):167-75. doi: 10.1016/j.jconrel.2012.06.013. Epub 2012 Jun 16.

引用本文的文献

1
mRNA and Adenoviral Vector Vaccine Platforms Utilized in COVID-19 Vaccines: Technologies, Ecosystem, and Future Directions.用于新冠疫苗的信使核糖核酸和腺病毒载体疫苗平台：技术、生态系统及未来方向
Vaccines (Basel). 2023 Nov 21;11(12):1737. doi: 10.3390/vaccines11121737.
2
Oncolytic virus: A catalyst for the treatment of gastric cancer.溶瘤病毒：一种用于治疗胃癌的催化剂。
Front Oncol. 2022 Nov 24;12:1017692. doi: 10.3389/fonc.2022.1017692. eCollection 2022.
3
Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs.

本文引用的文献

1
Cell cycle dependent transcription, a determinant factor of heterogeneity in cationic lipid-mediated transgene expression.细胞周期依赖性转录，阳离子脂质介导的转基因表达异质性的一个决定性因素。
J Gene Med. 2007 Mar;9(3):197-207. doi: 10.1002/jgm.1010.
2
Cellular uptake and subsequent intracellular trafficking of R8-liposomes introduced at low temperature.低温下引入的R8脂质体的细胞摄取及随后的细胞内运输。
Biochim Biophys Acta. 2006 Jun;1758(6):713-20. doi: 10.1016/j.bbamem.2006.04.015. Epub 2006 May 5.
3
Binding modes of the precursor of adenovirus major core protein VII to DNA and template activating factor I: implication for the mechanism of remodeling of the adenovirus chromatin.
了解核酸和基因药物的体内命运以进行药物的合理设计。
Pharmaceutics. 2021 Jan 26;13(2):159. doi: 10.3390/pharmaceutics13020159.
4
Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB.血脑屏障靶向性中枢神经系统基因递送的现状与挑战
Pharmaceutics. 2020 Dec 15;12(12):1216. doi: 10.3390/pharmaceutics12121216.
5
Role of Cellular Retention and Intracellular State in Controlling Gene Delivery Efficiency of Multiple Nonviral Carriers.细胞滞留和细胞内状态在控制多种非病毒载体基因递送效率中的作用
ACS Omega. 2019 Nov 26;4(24):20547-20557. doi: 10.1021/acsomega.9b02401. eCollection 2019 Dec 10.
6
Low Electric Treatment activates Rho GTPase via Heat Shock Protein 90 and Protein Kinase C for Intracellular Delivery of siRNA.低强度电处理通过热休克蛋白 90 和蛋白激酶 C 激活 Rho GTPase，实现 siRNA 的细胞内递送。
Sci Rep. 2019 Mar 11;9(1):4114. doi: 10.1038/s41598-019-40904-z.
7
The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment.新型功能性核酸iRed在通过微弱电处理进行细胞质递送后可有效调控靶基因。
Sci Technol Adv Mater. 2016 Sep 16;17(1):554-562. doi: 10.1080/14686996.2016.1221726. eCollection 2016.
8
Glucocorticoid Cell Priming Enhances Transfection Outcomes in Adult Human Mesenchymal Stem Cells.糖皮质激素细胞预处理可提高成人骨髓间充质干细胞的转染效果。
Mol Ther. 2016 Feb;24(2):331-341. doi: 10.1038/mt.2015.195. Epub 2015 Oct 19.
9
Mechanistic evaluation of the transfection barriers involved in lipid-mediated gene delivery: interplay between nanostructure and composition.脂质介导的基因递送中涉及的转染屏障的机制评估：纳米结构与组成之间的相互作用
Biochim Biophys Acta. 2014 Mar;1838(3):957-67. doi: 10.1016/j.bbamem.2013.11.014. Epub 2013 Dec 1.
10
Investigation of siRNA Nanoparticle Formation Using Mono-Cationic Detergents and Its Use in Gene Silencing in Human HeLa Cells.使用单阳离子型去污剂研究 siRNA 纳米颗粒的形成及其在人宫颈癌细胞系 HeLa 中基因沉默的应用。
Cancers (Basel). 2013 Nov 1;5(4):1413-25. doi: 10.3390/cancers5041413.
腺病毒主要核心蛋白VII前体与DNA及模板激活因子I的结合模式：对腺病毒染色质重塑机制的启示
Biochemistry. 2006 Jan 10;45(1):303-13. doi: 10.1021/bi051248+.
4
Involvement of template-activating factor I/SET in transcription of adenovirus early genes as a positive-acting factor.模板激活因子I/SET作为一种正性作用因子参与腺病毒早期基因的转录。
J Virol. 2006 Jan;80(2):794-801. doi: 10.1128/JVI.80.2.794-801.2006.
5
Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems.腺病毒和脂质体系统之间细胞内运输和核转录的定量比较。
Mol Ther. 2006 Apr;13(4):786-94. doi: 10.1016/j.ymthe.2005.10.007. Epub 2005 Dec 20.
6
Non-linear pharmacodynamics in a non-viral gene delivery system: positive non-linear relationship between dose and transfection efficiency.非病毒基因递送系统中的非线性药效学：剂量与转染效率之间的正非线性关系。
J Control Release. 2006 Feb 21;110(3):605-9. doi: 10.1016/j.jconrel.2005.10.021. Epub 2005 Dec 19.
7
Evaluation of the nuclear delivery and intra-nuclear transcription of plasmid DNA condensed with micro (mu) and NLS-micro by cytoplasmic and nuclear microinjection: a comparative study with poly-L-lysine.通过细胞质和细胞核显微注射对与微（μ）和核定位信号-微（NLS-μ）凝聚的质粒DNA的核递送和核内转录进行评估：与聚-L-赖氨酸的比较研究
J Gene Med. 2006 Feb;8(2):198-206. doi: 10.1002/jgm.839.
8
Targeting viral-mediated transduction to the lung airway epithelium with the anti-inflammatory cationic lipid dexamethasone-spermine.利用抗炎阳离子脂质地塞米松-精胺将病毒介导的转导靶向肺气道上皮细胞。
Mol Ther. 2005 Sep;12(3):502-9. doi: 10.1016/j.ymthe.2005.03.033.
9
Quantitative comparison of polyethylenimine formulations and adenoviral vectors in terms of intracellular gene delivery processes.聚乙烯亚胺制剂与腺病毒载体在细胞内基因递送过程方面的定量比较。
Gene Ther. 2005 Jul;12(13):1023-32. doi: 10.1038/sj.gt.3302495.
10
Evaluation of nuclear transfer and transcription of plasmid DNA condensed with protamine by microinjection: the use of a nuclear transfer score.通过显微注射评估与鱼精蛋白凝聚的质粒DNA的核转移和转录：核转移评分的应用。
FEBS Lett. 2005 Apr 11;579(10):2143-8. doi: 10.1016/j.febslet.2005.02.071.