混合骨架寡核苷酸作为第二代反义寡核苷酸：体外和体内研究
Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in vivo studies.
作者信息
Agrawal S, Jiang Z, Zhao Q, Shaw D, Cai Q, Roskey A, Channavajjala L, Saxinger C, Zhang R
机构信息
Hybridon Inc., Cambridge, MA 02139, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2620-5. doi: 10.1073/pnas.94.6.2620.
Abstract
Antisense oligonucleotides are being evaluated in clinical trials as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have designed mixed-backbone oligonucleotides (MBOs) that contain phosphorothioate segments at the 3' and 5' ends and have a modified oligodeoxynucleotide or oligoribonucleotide segment located in the central portion of the oligonucleotide. Some of these MBOs indicate improved properties compared with phosphorothioate oligodeoxynucleotides with respect to affinity to RNA, RNase H activation, and anti-HIV activity. In addition, more acceptable pharmacological, in vivo degradation and pharmacokinetic profiles were obtained with these MBOs.
摘要
反义寡核苷酸正在作为新型治疗药物进行临床试验评估。为了进一步改善反义寡核苷酸的特性，我们设计了混合骨架寡核苷酸（MBO），其在3'和5'末端含有硫代磷酸酯片段，并在寡核苷酸的中央部分含有修饰的寡脱氧核苷酸或寡核糖核苷酸片段。与硫代磷酸酯寡脱氧核苷酸相比，其中一些MBO在与RNA的亲和力、RNase H激活和抗HIV活性方面表现出改善的特性。此外，这些MBO获得了更可接受的药理学、体内降解和药代动力学特征。
相似文献
1
Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in vivo studies.混合骨架寡核苷酸作为第二代反义寡核苷酸：体外和体内研究
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2620-5. doi: 10.1073/pnas.94.6.2620.
2
Self-stabilized antisense oligodeoxynucleotide phosphorothioates: properties and anti-HIV activity.自稳定反义寡脱氧核苷酸硫代磷酸酯：性质与抗HIV活性
Nucleic Acids Res. 1993 Jun 11;21(11):2729-35. doi: 10.1093/nar/21.11.2729.
3
Mixed backbone antisense oligonucleotides: design, biochemical and biological properties of oligonucleotides containing 2'-5'-ribo- and 3'-5'-deoxyribonucleotide segments.混合主链反义寡核苷酸：含2'-5'-核糖核苷酸和3'-5'-脱氧核糖核苷酸片段的寡核苷酸的设计、生化及生物学特性
Nucleic Acids Res. 1997 Jan 15;25(2):370-8. doi: 10.1093/nar/25.2.370.
4
Inhibition of HIV-1 replication by foldback triple-helix forming oligonucleotides.通过回折三链螺旋形成寡核苷酸抑制HIV-1复制。
Nucleic Acids Symp Ser. 1997(37):221-2.
5
Inhibition of HIV-1 replication by a new type of circular dumbbell RNA/DNA chimeric oligonucleotides.新型环状哑铃状RNA/DNA嵌合寡核苷酸对HIV-1复制的抑制作用
Biochem Biophys Res Commun. 2000 Apr 21;270(3):953-60. doi: 10.1006/bbrc.2000.2542.
6
Inhibition of HIV-1 replication by triple-helix-forming phosphorothioate oligonucleotides targeted to the polypurine tract.靶向多聚嘌呤序列的三链形成硫代磷酸酯寡核苷酸对HIV-1复制的抑制作用
Biochem Biophys Res Commun. 1997 Apr 28;233(3):742-7. doi: 10.1006/bbrc.1997.6536.
7
Antisense oligonucleotides in solution or encapsulated in immunoliposomes inhibit replication of HIV-1 by several different mechanisms.溶液中的反义寡核苷酸或包裹在免疫脂质体中的反义寡核苷酸通过几种不同机制抑制HIV-1的复制。
Nucleic Acids Res. 1994 Oct 11;22(20):4307-14. doi: 10.1093/nar/22.20.4307.
8
Hairpin antisense oligonucleotides containing 2'-methoxynucleosides with base-pairing in the stem region at the 3'-end: penetration, localization, and Anti-HIV activity.在3'端茎区具有碱基配对的含2'-甲氧基核苷的发夹反义寡核苷酸：穿透、定位及抗HIV活性
Biochem Biophys Res Commun. 1996 Nov 12;228(2):623-31. doi: 10.1006/bbrc.1996.1707.
9
In vitro and in vivo transport and delivery of phosphorothioate oligonucleotides with cationic liposomes.阳离子脂质体介导硫代磷酸寡核苷酸的体外及体内转运与递送
Antivir Chem Chemother. 2004 Mar;15(2):93-100. doi: 10.1177/095632020401500205.
10
Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells.与Gag mRNA互补的硫代磷酸反义寡脱氧核苷酸可阻断1型人类免疫缺陷病毒在人外周血细胞中的复制。
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7942-6. doi: 10.1073/pnas.91.17.7942.
引用本文的文献
1
Clinical Applications of Antisense Oligonucleotides in Cancer: A Focus on Glioblastoma.反义寡核苷酸在癌症中的临床应用：以神经胶质瘤为例。
Cells. 2024 Nov 11;13(22):1869. doi: 10.3390/cells13221869.
2
Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system.量化和减轻中枢神经系统中反义寡核苷酸诱导的运动表型。
Mol Ther. 2024 Dec 4;32(12):4401-4417. doi: 10.1016/j.ymthe.2024.10.024. Epub 2024 Oct 28.
3
Therapeutic targeting of RNA for neurological and neuromuscular disease.RNA 靶向治疗在神经和神经肌肉疾病中的应用。
Genes Dev. 2024 Sep 19;38(15-16):698-717. doi: 10.1101/gad.351612.124.
4
The Dawning of a New Enterprise: RNA Therapeutics for the Skin.新事业的曙光：用于皮肤的RNA疗法
J Dermatol Skin Sci. 2023;5(1):4-13. doi: 10.29245/2767-5092/2023/1.1168. Epub 2023 Mar 9.
5
Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease?靶向脂蛋白(a)：RNA疗法能否成为预防心血管疾病的下一步方案？
Cardiol Ther. 2024 Mar;13(1):39-67. doi: 10.1007/s40119-024-00353-w. Epub 2024 Feb 21.
6
Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.靶向 RNA 的合成寡核苷酸：临床成功带来新的挑战。
Cell Chem Biol. 2024 Jan 18;31(1):125-138. doi: 10.1016/j.chembiol.2023.09.005. Epub 2023 Oct 6.
7
Antisense Therapy for Infectious Diseases.反义疗法治疗传染病。
Cells. 2023 Aug 21;12(16):2119. doi: 10.3390/cells12162119.
8
Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development.药物代谢与药代动力学科学在药物发现与开发中的翻译研究新进展。
Acta Pharm Sin B. 2022 Jun;12(6):2751-2777. doi: 10.1016/j.apsb.2022.03.009. Epub 2022 Mar 17.
9
Evaluation of DNA segments in 2'-modified RNA sequences in designing efficient splice switching antisense oligonucleotides.在设计高效剪接转换反义寡核苷酸时对2'-修饰RNA序列中的DNA片段进行评估。
RSC Adv. 2021 Apr 13;11(23):14029-14035. doi: 10.1039/d1ra00878a.
10
Introduction and History of the Chemistry of Nucleic Acids Therapeutics.核酸治疗药物化学的介绍和历史。
Methods Mol Biol. 2022;2434:3-31. doi: 10.1007/978-1-0716-2010-6_1.
本文引用的文献
1
Effects of synthetic oligonucleotides on human complement and coagulation.合成寡核苷酸对人体补体和凝血的影响。
Biochem Pharmacol. 1997 Apr 25;53(8):1123-32. doi: 10.1016/s0006-2952(97)00091-9.
2
Antisense oligonucleotides: towards clinical trials.反义寡核苷酸：迈向临床试验
Trends Biotechnol. 1996 Oct;14(10):376-87. doi: 10.1016/0167-7799(96)10053-6.
3
Pharmacokinetics and tissue disposition of a chimeric oligodeoxynucleoside phosphorothioate in rats after intravenous administration.静脉注射后，一种嵌合寡脱氧核苷硫代磷酸酯在大鼠体内的药代动力学和组织分布
J Pharmacol Exp Ther. 1996 Aug;278(2):971-9.
4
Effect of different chemically modified oligodeoxynucleotides on immune stimulation.不同化学修饰的寡脱氧核苷酸对免疫刺激的影响。
Biochem Pharmacol. 1996 Jan 26;51(2):173-82. doi: 10.1016/0006-2952(95)02177-9.
5
Novel enzymatic and immunological responses to oligonucleotides.对寡核苷酸的新型酶促和免疫反应。
Toxicol Lett. 1995 Dec;82-83:431-4. doi: 10.1016/0378-4274(95)03573-7.
6
Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells.与Gag mRNA互补的硫代磷酸反义寡脱氧核苷酸可阻断1型人类免疫缺陷病毒在人外周血细胞中的复制。
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7942-6. doi: 10.1073/pnas.91.17.7942.
7
In vivo toxicological effects of rel A antisense phosphorothioates in CD-1 mice.Rel A反义硫代磷酸酯在CD-1小鼠体内的毒理学效应。
Antisense Res Dev. 1994 Summer;4(2):99-107. doi: 10.1089/ard.1994.4.99.
8
Complement activation and hemodynamic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey.猴子静脉注射硫代磷酸酯寡核苷酸后的补体激活和血流动力学变化。
Antisense Res Dev. 1994 Fall;4(3):201-6. doi: 10.1089/ard.1994.4.201.
9
Large-scale synthesis, purification, and analysis of oligodeoxynucleotide phosphorothioates.寡脱氧核苷酸硫代磷酸酯的大规模合成、纯化及分析
Antisense Res Dev. 1994 Fall;4(3):185-99. doi: 10.1089/ard.1994.4.185.
10
Pharmacokinetics and tissue distribution in rats of an oligodeoxynucleotide phosphorothioate (GEM 91) developed as a therapeutic agent for human immunodeficiency virus type-1.一种作为人类免疫缺陷病毒1型治疗剂开发的硫代磷酸寡脱氧核苷酸（GEM 91）在大鼠体内的药代动力学和组织分布。
Biochem Pharmacol. 1995 Mar 30;49(7):929-39. doi: 10.1016/0006-2952(95)00010-w.
Zotero 插件