通过 DNA 骨干刷状聚合物提高寡核苷酸的酶稳定性和药代动力学特性。
Improving the Enzymatic Stability and the Pharmacokinetics of Oligonucleotides via DNA-Backboned Bottlebrush Polymers.
机构信息
Department of Chemistry and Chemical Biology , Northeastern University , Boston , Massachusetts 02115 , United States.
出版信息
Nano Lett. 2018 Nov 14;18(11):7378-7382. doi: 10.1021/acs.nanolett.8b03662. Epub 2018 Nov 2.
Abstract
Herein, we design and synthesize site-specifically PEGylated oligonucleotide hairpins and demonstrate that their ability to undergo hybridization chain reaction is nearly unaffected by the PEGylation. The resulting DNA-backboned bottlebrush polymers with PEG side chains exhibit increased resistance against nucleolytic degradation, enhanced thermal stabilities, and elevated blood retention times in vivo, which collectively pave the way for more therapeutically focused DNA nanostructure designs.
摘要
在此，我们设计并合成了定点 PEG 化的寡核苷酸发夹，并证明其杂交链式反应能力几乎不受 PEG 化的影响。所得的具有 PEG 侧链的 DNA 骨架刷状聚合物具有更高的抗核酸酶降解能力、增强的热稳定性和体内更长的血液保留时间，这为更具治疗重点的 DNA 纳米结构设计铺平了道路。
相似文献
1
Improving the Enzymatic Stability and the Pharmacokinetics of Oligonucleotides via DNA-Backboned Bottlebrush Polymers.通过 DNA 骨干刷状聚合物提高寡核苷酸的酶稳定性和药代动力学特性。
Nano Lett. 2018 Nov 14;18(11):7378-7382. doi: 10.1021/acs.nanolett.8b03662. Epub 2018 Nov 2.
2
Self-Assembled DNA-PEG Bottlebrushes Enhance Antisense Activity and Pharmacokinetics of Oligonucleotides.自组装 DNA-PEG 瓶刷增强寡核苷酸的反义活性和药代动力学。
ACS Appl Mater Interfaces. 2020 Oct 14;12(41):45830-45837. doi: 10.1021/acsami.0c13995. Epub 2020 Sep 30.
3
A Long-Circulating Vector for Aptamers Based upon Polyphosphodiester-Backboned Molecular Brushes.基于聚磷酸二酯骨架分子刷的适体长循环载体。
Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202204576. doi: 10.1002/anie.202204576. Epub 2022 Sep 6.
4
Effect of PEG Architecture on the Hybridization Thermodynamics and Protein Accessibility of PEGylated Oligonucleotides.PEG 结构对聚乙二醇化寡核苷酸杂交热力学和蛋白质可及性的影响。
Angew Chem Int Ed Engl. 2017 Jan 24;56(5):1239-1243. doi: 10.1002/anie.201610753. Epub 2016 Dec 29.
5
Comparison of PEGylated and non-PEGylated proticles: An in vitro and in vivo study.聚乙二醇化和非聚乙二醇化颗粒的比较：一项体内外研究。
Eur J Pharm Sci. 2019 Nov 1;139:105063. doi: 10.1016/j.ejps.2019.105063. Epub 2019 Sep 2.
6
Therapeutic oligonucleotides with polyethylene glycol modifications.具有聚乙二醇修饰的治疗性寡核苷酸。
Future Med Chem. 2015;7(13):1721-31. doi: 10.4155/fmc.15.94. Epub 2015 Sep 29.
7
Enzymatic formation of PEGylated oligonucleotides.PEG 化寡核苷酸的酶促合成。
Bioconjug Chem. 2014 Feb 19;25(2):433-41. doi: 10.1021/bc400569z. Epub 2014 Feb 3.
8
PEGylated Amphiphilic Gd-DOTA Backboned-Bound Branched Polymers as Magnetic Resonance Imaging Contrast Agents.聚乙二醇化两亲性钆-多胺多羧基大环配体键合支化聚合物作为磁共振成像造影剂
Biomacromolecules. 2023 Dec 11;24(12):5998-6008. doi: 10.1021/acs.biomac.3c00987. Epub 2023 Nov 9.
9
Physicochemical and biological characterization of polyethylenimine-graft-poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides and ribozymes.聚乙烯亚胺接枝聚乙二醇嵌段共聚物作为寡核苷酸和核酶递送系统的物理化学及生物学特性
Bioconjug Chem. 2004 Jul-Aug;15(4):677-84. doi: 10.1021/bc034160m.
10
Bottlebrush Polymers Based on RAFT and the "C1" Polymerization Method: Controlled Synthesis and Application in Anticancer Drug Delivery.基于 RAFT 和“C1”聚合方法的瓶刷聚合物：可控合成及其在抗癌药物传递中的应用。
ACS Macro Lett. 2022 Feb 15;11(2):179-185. doi: 10.1021/acsmacrolett.1c00706. Epub 2022 Jan 13.
引用本文的文献
1
Generation of topologically defined linear and cyclic DNA bottle brush polymers a graft-to approach.拓扑定义的线性和环状DNA瓶刷聚合物的生成：一种接枝法。
Polym Chem. 2025 May 1. doi: 10.1039/d5py00082c.
2
A Fluorogenic Sensor via Catalytic Hairpin Assembly for Precise Live-Cell Imaging of mRNA.基于催化发夹组装的荧光传感器用于精确活细胞 mRNA 成像。
Methods Mol Biol. 2025;2875:165-175. doi: 10.1007/978-1-0716-4248-1_14.
3
RNA-Polymer Hybrids via Direct and Site-Selective Acylation with the ATRP Initiator and Photoinduced Polymerization.通过与原子转移自由基聚合引发剂的直接和选择性酰化以及光聚合反应生成 RNA 聚合酶杂交体
J Am Chem Soc. 2023 Jul 5;145(26):14435-14445. doi: 10.1021/jacs.3c03757. Epub 2023 Jun 26.
4
Targeting oncogenic KRAS with molecular brush-conjugated antisense oligonucleotides.用分子刷偶联反义寡核苷酸靶向致癌 KRAS。
Proc Natl Acad Sci U S A. 2022 Jul 19;119(29):e2113180119. doi: 10.1073/pnas.2113180119. Epub 2022 Jul 14.
5
Functional DNA-Polymer Conjugates.功能性DNA-聚合物共轭物
Chem Rev. 2021 Sep 22;121(18):11030-11084. doi: 10.1021/acs.chemrev.0c01074. Epub 2021 Mar 19.
6
Self-Assembled DNA-PEG Bottlebrushes Enhance Antisense Activity and Pharmacokinetics of Oligonucleotides.自组装 DNA-PEG 瓶刷增强寡核苷酸的反义活性和药代动力学。
ACS Appl Mater Interfaces. 2020 Oct 14;12(41):45830-45837. doi: 10.1021/acsami.0c13995. Epub 2020 Sep 30.
7
Electrostatically PEGylated DNA enables salt-free hybridization in water.静电聚乙二醇化的DNA可实现水中无盐杂交。
Chem Sci. 2019 Sep 12;10(43):10097-10105. doi: 10.1039/c9sc02598g. eCollection 2019 Nov 21.
8
Expanding the materials space of DNA via organic-phase ring-opening metathesis polymerization.通过有机相开环易位聚合扩展DNA的材料空间。
Chem. 2019 Jun 13;5(6):1584-1596. doi: 10.1016/j.chempr.2019.03.023. Epub 2019 Apr 22.
本文引用的文献
1
PEGylation of therapeutic oligonucletides: From linear to highly branched PEG architectures.治疗性寡核苷酸的聚乙二醇化：从线性到高度分支的聚乙二醇结构
Nano Res. 2018 Oct;11(10):5519-5534. doi: 10.1007/s12274-018-2131-8. Epub 2018 Jul 6.
2
Modulating the Depolymerization of Self-Immolative Brush Polymers with Poly(benzyl ether) Backbones.调控具有聚（苄基醚）主链的自牺牲刷状聚合物的解聚作用
Macromolecules. 2018 Apr 24;51(8):2899-2905. doi: 10.1021/acs.macromol.8b00208. Epub 2018 Apr 3.
3
3D DNA Origami Crystals.3D DNA 折纸晶体。
Adv Mater. 2018 Jul;30(28):e1800273. doi: 10.1002/adma.201800273. Epub 2018 May 18.
4
Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns.具有任意图案的微米级 DNA 折纸阵列的分形组装。
Nature. 2017 Dec 6;552(7683):67-71. doi: 10.1038/nature24655.
5
Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)-DNA Conjugates.深度剖析具有刷状结构的聚乙二醇 -DNA 缀合物的核酸酶稳定性和基因沉默效果。
J Am Chem Soc. 2017 Aug 9;139(31):10605-10608. doi: 10.1021/jacs.7b05064. Epub 2017 Jul 26.
6
Modulating the Cellular Immune Response of Oligonucleotides by Brush Polymer-Assisted Compaction.通过刷状聚合物辅助紧缩调节寡核苷酸的细胞免疫反应。
Small. 2017 Nov;13(43). doi: 10.1002/smll.201701432. Epub 2017 Jul 11.
7
DNA Origami: Scaffolds for Creating Higher Order Structures.DNA 折纸术：创建更高阶结构的支架。
Chem Rev. 2017 Oct 25;117(20):12584-12640. doi: 10.1021/acs.chemrev.6b00825. Epub 2017 Jun 12.
8
Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation.基于寡聚赖氨酸的涂层可防止 DNA 纳米结构在低盐下变性和核酸酶降解。
Nat Commun. 2017 May 31;8:15654. doi: 10.1038/ncomms15654.
9
Effect of PEG Architecture on the Hybridization Thermodynamics and Protein Accessibility of PEGylated Oligonucleotides.PEG 结构对聚乙二醇化寡核苷酸杂交热力学和蛋白质可及性的影响。
Angew Chem Int Ed Engl. 2017 Jan 24;56(5):1239-1243. doi: 10.1002/anie.201610753. Epub 2016 Dec 29.
10
Precise Coating of a Wide Range of DNA Templates by a Protein Polymer with a DNA Binding Domain.通过具有 DNA 结合结构域的蛋白质聚合物对广泛范围的 DNA 模板进行精确涂层。
ACS Nano. 2017 Jan 24;11(1):144-152. doi: 10.1021/acsnano.6b05938. Epub 2016 Dec 12.
Zotero 插件