一种有潜力使锤头核酶疗法重新焕发生机的发现，可用于治疗遗传性视网膜退行性疾病。
A Discovery with Potential to Revitalize Hammerhead Ribozyme Therapeutics for Treatment of Inherited Retinal Degenerations.
机构信息
Research Service, VA Western NY Healthcare System, Departments of Ophthalmology (Ross Eye Institute), Pharmacology/Toxicology, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
Research Service, VA Western NY Healthcare System, Department of Ophthalmology (Ross Eye Institute), University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
出版信息
Adv Exp Med Biol. 2019;1185:119-124. doi: 10.1007/978-3-030-27378-1_20.
Abstract
Hammerhead ribozymes (hhRzs), RNA enzymes capable of site-specific cleavage of arbitrary target mRNAs, have faced significant hurdles in development and optimization as gene therapeutics for clinical translation. Chemical and biological barriers must be overcome to realize an effective therapeutic. A new Facilitated ribozyme has been identified with greatly enhanced kinetic properties that lead new insight on the capacity of ribozymes to target mutant genes to treat inherited retinal degenerations.
摘要
锤头状核酶（hhRzs）是一种能够特异性切割任意靶标 mRNA 的 RNA 酶，作为基因治疗药物在临床转化方面的发展和优化面临着重大的障碍。为了实现有效的治疗，必须克服化学和生物学的障碍。一种新的促进核酶被发现具有大大增强的动力学特性，这为核酶靶向突变基因治疗遗传性视网膜退行性疾病的能力提供了新的见解。
相似文献
1
A Discovery with Potential to Revitalize Hammerhead Ribozyme Therapeutics for Treatment of Inherited Retinal Degenerations.一种有潜力使锤头核酶疗法重新焕发生机的发现，可用于治疗遗传性视网膜退行性疾病。
Adv Exp Med Biol. 2019;1185:119-124. doi: 10.1007/978-3-030-27378-1_20.
2
A cellular high-throughput screening approach for therapeutic trans-cleaving ribozymes and RNAi against arbitrary mRNA disease targets.一种针对治疗性反式切割核酶和针对任意mRNA疾病靶点的RNA干扰的细胞高通量筛选方法。
Exp Eye Res. 2016 Oct;151:236-55. doi: 10.1016/j.exer.2016.05.020. Epub 2016 May 25.
3
Development of lead hammerhead ribozyme candidates against human rod opsin mRNA for retinal degeneration therapy.开发针对人视杆细胞视蛋白mRNA的锤头状核酶候选物用于视网膜变性治疗。
Exp Eye Res. 2009 May;88(5):859-79. doi: 10.1016/j.exer.2008.11.018. Epub 2008 Dec 6.
4
5
Ribozyme-based therapeutic approaches for autosomal dominant retinitis pigmentosa.基于核酶的常染色体显性遗传性视网膜色素变性治疗方法。
Invest Ophthalmol Vis Sci. 2000 Sep;41(10):2863-9.
6
Ribozyme-targeted destruction of RNA associated with autosomal-dominant retinitis pigmentosa.针对与常染色体显性遗传性视网膜色素变性相关的RNA的核酶靶向破坏
Invest Ophthalmol Vis Sci. 1998 Apr;39(5):681-9.
7
Ribozyme knockdown of the gamma-subunit of rod cGMP phosphodiesterase alters the ERG and retinal morphology in wild-type mice.通过核酶敲低视杆细胞环鸟苷酸磷酸二酯酶的γ亚基会改变野生型小鼠的视网膜电图和视网膜形态。
Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3836-44. doi: 10.1167/iovs.04-1283.
8
9
Ribozymes in the age of molecular therapeutics.分子治疗时代的核酶
Curr Mol Med. 2004 Aug;4(5):489-506. doi: 10.2174/1566524043360410.
10
Hammerhead ribozymes targeted to the FBN1 mRNA can discriminate a single base mismatch between ribozyme and target.靶向FBN1 mRNA的锤头状核酶能够区分核酶与靶标之间的单个碱基错配。
Biochem Biophys Res Commun. 1998 Aug 28;249(3):804-10. doi: 10.1006/bbrc.1998.9241.
引用本文的文献
1
Therapeutic applications of RNA nanostructures.RNA纳米结构的治疗应用。
RSC Adv. 2024 Sep 11;14(39):28807-28821. doi: 10.1039/d4ra03823a. eCollection 2024 Sep 4.
2
Advancements in clinical RNA therapeutics: Present developments and prospective outlooks.临床 RNA 治疗学的进展：现状与展望。
Cell Rep Med. 2024 May 21;5(5):101555. doi: 10.1016/j.xcrm.2024.101555. Epub 2024 May 13.
3
Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1.1 型肌强直性营养不良反义疗法的研究进展与挑战
Int J Mol Sci. 2022 Nov 1;23(21):13359. doi: 10.3390/ijms232113359.
4
Structural variants and modifications of hammerhead ribozymes targeting influenza A virus conserved structural motifs.靶向甲型流感病毒保守结构基序的锤头状核酶的结构变体与修饰
Mol Ther Nucleic Acids. 2022 May 31;29:64-74. doi: 10.1016/j.omtn.2022.05.035. eCollection 2022 Sep 13.
5
The Next Generation of Molecular and Cellular Therapeutics for Inherited Retinal Disease.遗传性视网膜疾病的新一代分子和细胞治疗方法。
Int J Mol Sci. 2021 Oct 26;22(21):11542. doi: 10.3390/ijms222111542.
6
Paving the Road for RNA Therapeutics.为 RNA 治疗学铺平道路。
Trends Pharmacol Sci. 2020 Oct;41(10):755-775. doi: 10.1016/j.tips.2020.08.004. Epub 2020 Sep 3.
本文引用的文献
1
Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector.通过使用单个 AAV 载体进行敲低和替换实现不依赖突变的视紫红质基因治疗。
Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8547-E8556. doi: 10.1073/pnas.1805055115. Epub 2018 Aug 20.
2
Effects of Pathogenic Variations in the Human Rhodopsin Gene (hRHO) on the Predicted Accessibility for a Lead Candidate Ribozyme.人类视紫红质基因（hRHO）中的致病变异对一种潜在候选核酶预测可及性的影响。
Invest Ophthalmol Vis Sci. 2017 Jul 1;58(9):3576-3591. doi: 10.1167/iovs.16-20877.
3
HIV and Ribozymes.艾滋病病毒与核酶
Adv Exp Med Biol. 2015;848:97-116. doi: 10.1007/978-1-4939-2432-5_5.
4
Variables and strategies in development of therapeutic post-transcriptional gene silencing agents.治疗性转录后基因沉默剂开发中的变量与策略
J Ophthalmol. 2011;2011:531380. doi: 10.1155/2011/531380. Epub 2011 Jun 30.
5
Enhanced product stability in the hammerhead ribozyme.锤头核酶的增强产物稳定性。
Biochemistry. 2010 Jun 1;49(21):4494-500. doi: 10.1021/bi902025m.
6
Highly active low magnesium hammerhead ribozyme.高活性低镁锤头状核酶
J Biochem. 2009 Apr;145(4):451-9. doi: 10.1093/jb/mvn182. Epub 2009 Jan 4.
7
Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme.使用等位基因非依赖性核酶保存P23H大鼠的光感受器形态和功能。
Exp Eye Res. 2007 Jan;84(1):44-52. doi: 10.1016/j.exer.2006.08.014. Epub 2006 Nov 1.
8
Tertiary contacts distant from the active site prime a ribozyme for catalysis.远离活性位点的三级接触为核酶的催化作用做好准备。
Cell. 2006 Jul 28;126(2):309-20. doi: 10.1016/j.cell.2006.06.036. Epub 2006 Jul 20.
9
10
Peripheral regions of natural hammerhead ribozymes greatly increase their self-cleavage activity.天然锤头状核酶的外围区域极大地增强了它们的自我切割活性。
EMBO J. 2003 Oct 15;22(20):5561-70. doi: 10.1093/emboj/cdg530.
Zotero 插件