追踪用于基因递送的聚乙烯亚胺/DNA复合物的细胞内路径。
Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery.
作者信息
Godbey W T, Wu K K, Mikos A G
机构信息
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251-1892, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5177-81. doi: 10.1073/pnas.96.9.5177.
Abstract
Poly(ethylenimine) (PEI) is one of a number of polycations that has been used successfully to transfer genes into living cells. Although PEI shows promise in the field of gene therapy, to date no rigorous proof of mechanism has been published regarding the fate of PEI/DNA administered for transfection. Here we show, by using fluorescent labeling and confocal microscopy, the paths of PEI/DNA complexes from endocytosis to gene expression. We found that complexes attach to cell surfaces and migrate into clumps that are endocytosed. The endocytotic vesicles grow in number and size and are occasionally seen to lyse. Most interesting is the fact that endocytosed PEI, whether administered with or without DNA, undergoes nuclear localization in the form of ordered structures.
摘要
聚乙烯亚胺（PEI）是众多已成功用于将基因导入活细胞的聚阳离子之一。尽管PEI在基因治疗领域显示出前景，但迄今为止，尚未有关于用于转染的PEI/DNA命运的严格机制证明发表。在这里，我们通过使用荧光标记和共聚焦显微镜，展示了PEI/DNA复合物从内吞作用到基因表达的路径。我们发现复合物附着在细胞表面并迁移到被内吞的团块中。内吞小泡的数量和大小增加，偶尔可见其裂解。最有趣的是，无论是否与DNA一起施用，内吞的PEI都会以有序结构的形式进行核定位。
相似文献
1
Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery.追踪用于基因递送的聚乙烯亚胺/DNA复合物的细胞内路径。
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5177-81. doi: 10.1073/pnas.96.9.5177.
2
Poly(ethylenimine) and its role in gene delivery.聚乙烯亚胺及其在基因递送中的作用。
J Control Release. 1999 Aug 5;60(2-3):149-60. doi: 10.1016/s0168-3659(99)00090-5.
3
Conjugation of a new two-photon fluorophore to poly(ethylenimine) for gene delivery imaging.一种新型双光子荧光团与聚乙烯亚胺的共轭用于基因递送成像。
Bioconjug Chem. 2007 May-Jun;18(3):844-51. doi: 10.1021/bc060362h. Epub 2007 Apr 3.
4
Brush-shaped polycation with poly(ethylenimine)-b-poly(ethylene glycol) side chains as highly efficient gene delivery vector.具有聚（亚乙基亚胺）-b-聚（乙二醇）侧链的刷状聚阳离子作为高效基因传递载体。
Int J Pharm. 2010 Jun 15;392(1-2):118-26. doi: 10.1016/j.ijpharm.2010.03.043. Epub 2010 Mar 25.
5
Effect of peptides and their introduction methods on target gene transfer of gene vector based on disulfide-containing polyethyleneimine.基于含二硫键的聚乙烯亚胺的基因载体，肽及其引入方法对靶基因转导的影响。
Int J Pharm. 2012 Nov 15;438(1-2):191-201. doi: 10.1016/j.ijpharm.2012.08.039. Epub 2012 Aug 28.
6
Quantitative colocalization analysis of DNA delivery by PEI-mediated cationic polymers in mammalian cells.通过 PEI 介导的阳离子聚合物在哺乳动物细胞中进行 DNA 传递的定量共定位分析。
J Microsc. 2019 Jan;273(1):53-64. doi: 10.1111/jmi.12760. Epub 2018 Oct 8.
7
Enhancement of poly(orthoester) microspheres for DNA vaccine delivery by blending with poly(ethylenimine).通过与聚乙烯亚胺共混增强聚原酸酯微球用于DNA疫苗递送的性能
Biomaterials. 2008 Jun;29(18):2783-93. doi: 10.1016/j.biomaterials.2008.03.011. Epub 2008 Apr 9.
8
Role of endocytosis in the transfection of L929 fibroblasts by polyethylenimine/DNA complexes.内吞作用在聚乙烯亚胺/DNA复合物转染L929成纤维细胞中的作用
Biochim Biophys Acta. 2001 Sep 3;1514(1):21-32. doi: 10.1016/s0005-2736(01)00359-5.
9
Interaction of poly(ethylenimine)-DNA polyplexes with mitochondria: implications for a mechanism of cytotoxicity.聚（乙二亚胺）-DNA 复合物与线粒体的相互作用：对细胞毒性机制的影响。
Mol Pharm. 2011 Oct 3;8(5):1709-19. doi: 10.1021/mp200078n. Epub 2011 Jul 18.
10
Improved packing of poly(ethylenimine)/DNA complexes increases transfection efficiency.聚（乙烯亚胺）/DNA复合物包装的改进提高了转染效率。
Gene Ther. 1999 Aug;6(8):1380-8. doi: 10.1038/sj.gt.3300976.
引用本文的文献
1
Intensification of rAAV Production Based on HEK293 Cell Transient Transfection.基于HEK293细胞瞬时转染的重组腺相关病毒（rAAV）生产强化
Biotechnol J. 2025 Jun;20(6):e70020. doi: 10.1002/biot.70020.
2
Polyethyleneimine-mediated gene transfection in porcine fetal fibroblasts.聚乙烯亚胺介导的猪胎儿成纤维细胞基因转染
Anim Reprod. 2024 Nov 22;21(4):e20240026. doi: 10.1590/1984-3143-AR2024-0026. eCollection 2024.
3
Polymeric Vehicles for Nucleic Acid Delivery: Enhancing the Therapeutic Efficacy and Cellular Uptake.聚合物载体用于核酸递送：增强治疗效果和细胞摄取。
Recent Adv Drug Deliv Formul. 2024;18(4):276-293. doi: 10.2174/0126673878324536240805060143.
4
The intracellular visualization of exogenous DNA in fluorescence microscopy.在荧光显微镜下观察细胞内的外源 DNA。
Drug Deliv Transl Res. 2024 Aug;14(8):2242-2261. doi: 10.1007/s13346-024-01563-4. Epub 2024 Mar 25.
5
Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape.mRNA 纳米颗粒技术：递呈策略、临床应用和发展前景。
Theranostics. 2024 Jan 1;14(2):738-760. doi: 10.7150/thno.84291. eCollection 2024.
6
How does the polymer architecture and position of cationic charges affect cell viability?聚合物结构和阳离子电荷的位置如何影响细胞活力？
Polym Chem. 2022 Dec 7;14(3):303-317. doi: 10.1039/d2py01012g. eCollection 2023 Jan 17.
7
miR-122-5p Regulates Renal Fibrosis In Vivo.miR-122-5p 在体内调节肾纤维化。
Int J Mol Sci. 2022 Dec 6;23(23):15423. doi: 10.3390/ijms232315423.
8
A novel phosphoester-based cationic co-polymer nanocarrier delivers chimeric antigen receptor plasmid and exhibits anti-tumor effect.一种新型的基于磷酸酯的阳离子共聚物纳米载体可递送嵌合抗原受体质粒并展现出抗肿瘤作用。
RSC Adv. 2018 Apr 19;8(27):14975-14982. doi: 10.1039/c8ra02133c. eCollection 2018 Apr 18.
9
Designing electrospun fiber platforms for efficient delivery of genetic material and genome editing tools.设计用于高效传递遗传物质和基因组编辑工具的静电纺丝纤维平台。
Adv Drug Deliv Rev. 2022 Apr;183:114161. doi: 10.1016/j.addr.2022.114161. Epub 2022 Feb 17.
10
Polyethyleneimine-Based Lipopolyplexes as Carriers in Anticancer Gene Therapies.基于聚乙烯亚胺的脂质多聚体作为抗癌基因治疗中的载体
Materials (Basel). 2021 Dec 27;15(1):179. doi: 10.3390/ma15010179.
本文引用的文献
1
Size matters: molecular weight affects the efficiency of poly(ethylenimine) as a gene delivery vehicle.
J Biomed Mater Res. 1999 Jun 5;45(3):268-75. doi: 10.1002/(sici)1097-4636(19990605)45:3<268::aid-jbm15>3.0.co;2-q.
2
The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells.DNA/转铁蛋白-聚乙烯亚胺复合物的大小是影响培养细胞中基因表达的一个重要因素。
Gene Ther. 1998 Oct;5(10):1425-33. doi: 10.1038/sj.gt.3300745.
3
Effects of polyethyleneimine on endocytosis and lysosome stability.聚乙烯亚胺对胞吞作用和溶酶体稳定性的影响。
Biochem Pharmacol. 1998 Jul 1;56(1):41-6. doi: 10.1016/s0006-2952(98)00098-7.
4
Polyethylenimine but not cationic lipids promotes transgene delivery to the nucleus in mammalian cells.
J Biol Chem. 1998 Mar 27;273(13):7507-11. doi: 10.1074/jbc.273.13.7507.
5
Permeabilizing action of polyethyleneimine on Salmonella typhimurium involves disruption of the outer membrane and interactions with lipopolysaccharide.聚乙烯亚胺对鼠伤寒沙门氏菌的通透作用涉及外膜的破坏以及与脂多糖的相互作用。
Microbiology (Reading). 1998 Feb;144 ( Pt 2):385-390. doi: 10.1099/00221287-144-2-385.
6
Polyethyleneimine is an effective permeabilizer of gram-negative bacteria.聚乙烯亚胺是一种有效的革兰氏阴性菌通透剂。
Microbiology (Reading). 1997 Oct;143 ( Pt 10):3193-3199. doi: 10.1099/00221287-143-10-3193.
7
Nonviral gene delivery to the rat kidney with polyethylenimine.利用聚乙烯亚胺将非病毒基因导入大鼠肾脏。
Hum Gene Ther. 1997 Jul 1;8(10):1243-51. doi: 10.1089/hum.1997.8.10-1243.
8
Optimized galenics improve in vitro gene transfer with cationic molecules up to 1000-fold.优化的药剂学方法可使阳离子分子的体外基因转移效率提高至原来的1000倍。
Gene Ther. 1996 Dec;3(12):1074-80.
9
A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: polyethylenimine.一种用于成年哺乳动物脑内体内基因转移的强大非病毒载体：聚乙烯亚胺。
Hum Gene Ther. 1996 Oct 20;7(16):1947-54. doi: 10.1089/hum.1996.7.16-1947.
10
Polyethylenimine-mediated DNA transfection of peripheral and central neurons in primary culture: probing Ca2+ channel structure and function with antisense oligonucleotides.聚乙烯亚胺介导的原代培养外周和中枢神经元的DNA转染：用反义寡核苷酸探测钙通道的结构和功能
Mol Cell Neurosci. 1996 Mar;7(3):239-46. doi: 10.1006/mcne.1996.0018.
Zotero 插件