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
PEGylation of therapeutic oligonucletides: From linear to highly branched PEG architectures.
作者信息
Lu Xueguang, Zhang Ke
机构信息
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA.
出版信息
Nano Res. 2018 Oct;11(10):5519-5534. doi: 10.1007/s12274-018-2131-8. Epub 2018 Jul 6.
Abstract
PEGylation, the attachment of poly(ethylene glycol) (PEG), has been adopted to improve the pharmacokinetic properties of oligonucleotide therapeutics for nearly 30 years. Prior efforts mainly focused on the investigation of linear or slightly branched PEG having different molecular weights, terminal functional groups, and possible oligonucleotide sites for functionalization. Recent studies on highly branched PEG (including brush, star, and micellar structures) indicate superior properties in several areas including cellular uptake, gene regulation efficacy, reduction of side effects, and biodistribution. This review focuses on comparing the effects of PEG architecture on the physiochemical and biological properties of the PEGylated oligonucleotide.
摘要
聚乙二醇化，即连接聚乙二醇（PEG），已被用于改善寡核苷酸疗法的药代动力学特性近30年。此前的努力主要集中在研究具有不同分子量、末端官能团以及可能的寡核苷酸功能化位点的线性或轻度支化PEG。最近对高度支化PEG（包括刷状、星状和胶束结构）的研究表明，其在细胞摄取、基因调控效率、副作用减少和生物分布等几个方面具有优异特性。本综述着重比较PEG结构对聚乙二醇化寡核苷酸的物理化学和生物学特性的影响。
相似文献
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
Pharmacokinetic, biodistribution, and biophysical profiles of TNF nanobodies conjugated to linear or branched poly(ethylene glycol).TNF 纳米抗体与线性或支化聚乙二醇偶联的药代动力学、生物分布和生物物理特性。
Bioconjug Chem. 2012 Jul 18;23(7):1452-62. doi: 10.1021/bc300066a. Epub 2012 Jun 25.
3
Size comparison between proteins PEGylated with branched and linear poly(ethylene glycol) molecules.用支链和线性聚乙二醇分子聚乙二醇化的蛋白质之间的大小比较。
Biotechnol Bioeng. 2007 Nov 1;98(4):725-31. doi: 10.1002/bit.21482.
4
N-terminal specificity of PEGylation of human bone morphogenetic protein-2 at acidic pH.在酸性 pH 值下，人骨形态发生蛋白-2 的 PEGylation 的 N 端特异性。
Int J Pharm. 2011 Jul 15;413(1-2):140-6. doi: 10.1016/j.ijpharm.2011.04.043. Epub 2011 Apr 22.
5
High-Density Branched PEGylation for Nanoparticle Drug Delivery.用于纳米颗粒药物递送的高密度支链聚乙二醇化
Cell Mol Bioeng. 2022 Jul 5;15(5):355-366. doi: 10.1007/s12195-022-00727-x. eCollection 2022 Oct.
6
The impact of PEGylation on biological therapies.聚乙二醇化对生物疗法的影响。
BioDrugs. 2008;22(5):315-29. doi: 10.2165/00063030-200822050-00004.
7
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.
9
PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response.具有可逆抗凝活性和最小免疫反应的RNA适配体的聚乙二醇样刷状聚合物缀合物。
Adv Mater. 2022 Mar;34(10):e2107852. doi: 10.1002/adma.202107852. Epub 2022 Jan 31.
10
Clinical Relevance of Pre-Existing and Treatment-Induced Anti-Poly(Ethylene Glycol) Antibodies.预先存在的和治疗诱导的抗聚乙二醇抗体的临床相关性
Regen Eng Transl Med. 2022;8(1):32-42. doi: 10.1007/s40883-021-00198-y. Epub 2021 Mar 25.
引用本文的文献
1
Acidity Reversal Enables Site-Specific Ring-Opening Polymerization of Epoxides from Biprotonic Compounds.酸度反转实现了双质子化合物引发环氧化物的位点特异性开环聚合。
J Am Chem Soc. 2025 Feb 12;147(6):5189-5196. doi: 10.1021/jacs.4c15676. Epub 2025 Jan 22.
2
Bottlebrush Polymers with Sequence-Controlled Backbones for Enhanced Oligonucleotide Delivery.具有序列可控主链的瓶刷状聚合物用于增强寡核苷酸递送
J Am Chem Soc. 2024 Dec 18;146(50):34763-34770. doi: 10.1021/jacs.4c13285. Epub 2024 Nov 27.
3
Optimizing Pharmacological and Immunological Properties of Therapeutic Proteins Through PEGylation: Investigating Key Parameters and Their Impact.通过聚乙二醇化优化治疗性蛋白质的药理学和免疫学性质：研究关键参数及其影响。
Drug Des Devel Ther. 2024 Nov 7;18:5041-5062. doi: 10.2147/DDDT.S481420. eCollection 2024.
4
Novel Aptamer Strategies in Combating Bacterial Infections: From Diagnostics to Therapeutics.对抗细菌感染的新型适配体策略：从诊断到治疗
Pharmaceutics. 2024 Aug 29;16(9):1140. doi: 10.3390/pharmaceutics16091140.
5
Architectural engineering of Cyborg Bacteria with intracellular hydrogel.具有细胞内水凝胶的半机械人细菌的架构工程。
Mater Today Bio. 2024 Sep 6;28:101226. doi: 10.1016/j.mtbio.2024.101226. eCollection 2024 Oct.
6
Therapeutic Applications of Aptamers.适体的治疗应用。
Int J Mol Sci. 2024 Jun 19;25(12):6742. doi: 10.3390/ijms25126742.
7
RNA nanostructures for targeted drug delivery and imaging.RNA 纳米结构用于靶向药物递送和成像。
RNA Biol. 2024 Jan;21(1):1-19. doi: 10.1080/15476286.2024.2328440. Epub 2024 Mar 31.
8
Research progress on the PEGylation of therapeutic proteins and peptides (TPPs).治疗性蛋白质和肽（TPPs）的聚乙二醇化研究进展
Front Pharmacol. 2024 Mar 8;15:1353626. doi: 10.3389/fphar.2024.1353626. eCollection 2024.
9
Enabling safer, more potent oligonucleotide therapeutics with bottlebrush polymer conjugates.用瓶刷聚合物缀合物实现更安全、更有效的寡核苷酸治疗。
J Control Release. 2024 Feb;366:44-51. doi: 10.1016/j.jconrel.2023.12.035. Epub 2023 Dec 29.
10
Unravelling Surface Modification Strategies for Preventing Medical Device-Induced Thrombosis.解析用于预防医疗器械诱导血栓形成的表面改性策略。
Adv Healthc Mater. 2024 Jan;13(1):e2301039. doi: 10.1002/adhm.202301039. Epub 2023 Oct 5.
本文引用的文献
1
Synthesis and enzymatic stability of PEGylated oligonucleotide duplexes and their self-assemblies with polyamidoamine dendrimers.聚乙二醇化寡核苷酸双链体的合成及其酶稳定性，以及它们与聚酰胺胺树枝状大分子的自组装
Soft Matter. 2008 Jan 22;4(2):294-302. doi: 10.1039/b714221h.
2
Precision Tuning of DNA- and Poly(ethylene glycol)-Based Nanoparticles via Coassembly for Effective Antisense Gene Regulation.通过共组装对基于DNA和聚乙二醇的纳米颗粒进行精确调控以实现有效的反义基因调控
Chem Mater. 2017 Dec 12;29(23):9882-9886. doi: 10.1021/acs.chemmater.7b03520. Epub 2017 Nov 18.
3
Update on the clinical utility of an RNA interference-based treatment: focus on Patisiran.基于RNA干扰的治疗的临床效用最新进展：聚焦于帕替拉韦钠。
Pharmgenomics Pers Med. 2017 Nov 10;10:267-278. doi: 10.2147/PGPM.S87945. eCollection 2017.
4
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.
5
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.
6
FDA-Approved Oligonucleotide Therapies in 2017.2017年美国食品药品监督管理局批准的寡核苷酸疗法
Mol Ther. 2017 May 3;25(5):1069-1075. doi: 10.1016/j.ymthe.2017.03.023. Epub 2017 Mar 31.
7
Preclinical and Clinical Advances of GalNAc-Decorated Nucleic Acid Therapeutics.N-乙酰半乳糖胺修饰的核酸疗法的临床前和临床进展
Mol Ther Nucleic Acids. 2017 Mar 17;6:116-132. doi: 10.1016/j.omtn.2016.12.003. Epub 2016 Dec 10.
8
The chemical evolution of oligonucleotide therapies of clinical utility.具有临床应用价值的寡核苷酸疗法的化学进化
Nat Biotechnol. 2017 Mar;35(3):238-248. doi: 10.1038/nbt.3765. Epub 2017 Feb 27.
9
Nusinersen, an antisense oligonucleotide drug for spinal muscular atrophy.诺西那生钠，一种用于治疗脊髓性肌萎缩症的反义寡核苷酸药物。
Nat Neurosci. 2017 Apr;20(4):497-499. doi: 10.1038/nn.4508. Epub 2017 Feb 13.
10
Characterizing the effect of GalNAc and phosphorothioate backbone on binding of antisense oligonucleotides to the asialoglycoprotein receptor.表征N-乙酰半乳糖胺和硫代磷酸酯主链对反义寡核苷酸与去唾液酸糖蛋白受体结合的影响。
Nucleic Acids Res. 2017 Mar 17;45(5):2294-2306. doi: 10.1093/nar/gkx060.
Zotero 插件