慢病毒载体介导的中枢神经系统RNA沉默
Lentiviral vector-mediated RNA silencing in the central nervous system.
作者信息
Hutson Thomas H, Foster Edmund, Moon Lawrence D F, Yáñez-Muñoz Rafael J
机构信息
1 Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London , Guy's Campus, London SE1 1UL, United Kingdom .
出版信息
Hum Gene Ther Methods. 2014 Feb;25(1):14-32. doi: 10.1089/hgtb.2013.016. Epub 2013 Nov 1.
Abstract
RNA silencing is an established method for investigating gene function and has attracted particular interest because of the potential for generating RNA-based therapeutics. Using lentiviral vectors as an efficient delivery system that offers stable, long-term expression in postmitotic cells further enhances the applicability of an RNA-based gene therapy for the CNS. In this review we provide an overview of both lentiviral vectors and RNA silencing along with design considerations for generating lentiviral vectors capable of RNA silencing. We go on to describe the current preclinical data regarding lentiviral vector-mediated RNA silencing for CNS disorders and discuss the concerns of side effects associated with lentiviral vectors and small interfering RNAs and how these might be mitigated.
摘要
RNA沉默是一种用于研究基因功能的既定方法，由于具有生成基于RNA的疗法的潜力，它引起了特别的关注。使用慢病毒载体作为一种有效的递送系统，该系统可在有丝分裂后细胞中实现稳定、长期的表达，这进一步提高了基于RNA的基因疗法在中枢神经系统中的适用性。在这篇综述中，我们概述了慢病毒载体和RNA沉默，以及用于生成能够进行RNA沉默的慢病毒载体的设计考量。我们接着描述了目前关于慢病毒载体介导的RNA沉默用于中枢神经系统疾病的临床前数据，并讨论了与慢病毒载体和小干扰RNA相关的副作用问题，以及如何减轻这些问题。
相似文献
1
Lentiviral vector-mediated RNA silencing in the central nervous system.慢病毒载体介导的中枢神经系统RNA沉默
Hum Gene Ther Methods. 2014 Feb;25(1):14-32. doi: 10.1089/hgtb.2013.016. Epub 2013 Nov 1.
2
RNA interference-mediated silencing of SOCS-1 via lentiviral vector promotes apoptosis of alveolar epithelial cells in vitro.RNA 干扰介导的 SOCS-1 通过慢病毒载体沉默促进体外肺泡上皮细胞凋亡。
Mol Med Rep. 2012 Feb;5(2):452-6. doi: 10.3892/mmr.2011.672. Epub 2011 Nov 11.
3
Design and cloning of lentiviral vectors expressing small interfering RNAs.表达小干扰RNA的慢病毒载体的设计与克隆
Nat Protoc. 2006;1(1):234-40. doi: 10.1038/nprot.2006.36.
4
DNA vector-based RNA interference to study gene function in cancer.基于DNA载体的RNA干扰技术在癌症基因功能研究中的应用
J Vis Exp. 2012 Jun 4(64):e4129. doi: 10.3791/4129.
5
Lentiviral vector-mediated gene transfer and RNA silencing technology in neuronal dysfunctions.慢病毒载体介导的基因转移和 RNA 干扰技术在神经元功能障碍中的应用。
Mol Biotechnol. 2011 Feb;47(2):169-87. doi: 10.1007/s12033-010-9334-x.
6
Puromycin-resistant lentiviral control shRNA vector, pLKO.1 induces unexpected cellular differentiation of P19 embryonic stem cells.嘌呤霉素抗性慢病毒对照短发夹RNA载体pLKO.1可诱导P19胚胎干细胞发生意外的细胞分化。
Biochem Biophys Res Commun. 2017 Apr 29;486(2):481-485. doi: 10.1016/j.bbrc.2017.03.066. Epub 2017 Mar 16.
7
Lentiviral delivery of short hairpin RNAs.短发夹RNA的慢病毒递送
Adv Drug Deliv Rev. 2009 Jul 25;61(9):732-45. doi: 10.1016/j.addr.2009.03.004. Epub 2009 Mar 31.
8
Construction of p66Shc gene interfering lentivirus vectors and its effects on alveolar epithelial cells apoptosis induced by hyperoxia.p66Shc基因干扰慢病毒载体的构建及其对高氧诱导的肺泡上皮细胞凋亡的影响。
Drug Des Devel Ther. 2016 Aug 16;10:2611-22. doi: 10.2147/DDDT.S84820. eCollection 2016.
9
10
HIV-1 RRE RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs.HIV-1 RRE RNA 通过与TRBP结合的小干扰RNA竞争来充当RNA沉默抑制因子。
RNA Biol. 2015;12(2):123-35. doi: 10.1080/15476286.2015.1014759.
引用本文的文献
1
Nucleic Acid Armor: Fortifying RNA Therapeutics through Delivery and Targeting Innovations for Immunotherapy.核酸铠甲：通过递送和靶向创新增强 RNA 治疗免疫疗法。
Int J Mol Sci. 2024 Aug 15;25(16):8888. doi: 10.3390/ijms25168888.
2
[Research Progress of Engineered Exosomes in the Treatment of Lung Cancer].[工程化外泌体治疗肺癌的研究进展]
Zhongguo Fei Ai Za Zhi. 2024 Jul 20;27(7):535-540. doi: 10.3779/j.issn.1009-3419.2024.101.17.
3
Principle, application and challenges of development siRNA-based therapeutics against bacterial and viral infections: a comprehensive review.基于小干扰RNA的抗细菌和病毒感染疗法的原理、应用及发展挑战：综述
Front Microbiol. 2024 Jun 13;15:1393646. doi: 10.3389/fmicb.2024.1393646. eCollection 2024.
4
Engineering lentivirus envelope VSV-G for liver targeted delivery of IDOL-shRNA to ameliorate hypercholesterolemia and atherosclerosis.构建慢病毒包膜蛋白VSV-G用于将IDOL-shRNA靶向递送至肝脏，以改善高胆固醇血症和动脉粥样硬化。
Mol Ther Nucleic Acids. 2024 Jan 11;35(1):102115. doi: 10.1016/j.omtn.2024.102115. eCollection 2024 Mar 12.
5
Small interfering RNAs based therapies for intracerebral hemorrhage: challenges and progress in drug delivery systems.基于小干扰RNA的脑出血治疗：药物递送系统的挑战与进展
Neural Regen Res. 2022 Aug;17(8):1717-1725. doi: 10.4103/1673-5374.332129.
6
Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells.工程化靶向tLyp-1外泌体作为基因治疗载体用于将siRNA高效递送至肺癌细胞
Asian J Pharm Sci. 2020 Jul;15(4):461-471. doi: 10.1016/j.ajps.2019.04.002. Epub 2019 May 6.
7
Ex Vivo Rat Transected Spinal Cord Slices as a Model to Assess Lentiviral Vector Delivery of Neurotrophin-3 and Short Hairpin RNA against NG2.体外大鼠横断脊髓切片作为评估慢病毒载体递送神经营养因子-3和针对NG2的短发夹RNA的模型。
Biology (Basel). 2020 Mar 15;9(3):54. doi: 10.3390/biology9030054.
8
RNA Viruses as Tools in Gene Therapy and Vaccine Development.RNA 病毒在基因治疗和疫苗开发中的应用
Genes (Basel). 2019 Mar 1;10(3):189. doi: 10.3390/genes10030189.
9
Transcriptional Targeting and MicroRNA Regulation of Lentiviral Vectors.慢病毒载体的转录靶向与微小RNA调控
Mol Ther Methods Clin Dev. 2019 Jan 8;12:223-232. doi: 10.1016/j.omtm.2018.12.013. eCollection 2019 Mar 15.
10
The therapeutic effect in gliomas of nanobubbles carrying siRNA combined with ultrasound-targeted destruction.纳米气泡携带 siRNA 联合超声靶向破坏治疗脑胶质瘤的疗效。
Int J Nanomedicine. 2018 Oct 24;13:6791-6807. doi: 10.2147/IJN.S164760. eCollection 2018.
本文引用的文献
1
Biosafety features of lentiviral vectors.慢病毒载体的生物安全性特征。
Hum Gene Ther. 2013 Feb;24(2):132-42. doi: 10.1089/hum.2012.229.
2
Embedding siRNA sequences targeting apolipoprotein B100 in shRNA and miRNA scaffolds results in differential processing and in vivo efficacy.将靶向载脂蛋白 B100 的 siRNA 序列嵌入 shRNA 和 miRNA 支架中会导致不同的加工和体内疗效。
Mol Ther. 2013 Jan;21(1):217-27. doi: 10.1038/mt.2012.160. Epub 2012 Oct 23.
3
Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord.整合缺陷型慢病毒载体在脊髓中高效表达基因。
Gene Ther. 2013 Jun;20(6):645-57. doi: 10.1038/gt.2012.78. Epub 2012 Oct 18.
4
5
Small interfering RNA-mediated knockdown of NF-κBp65 attenuates neuropathic pain following peripheral nerve injury in rats.小干扰 RNA 介导的 NF-κBp65 敲低可减轻大鼠周围神经损伤后的神经病理性疼痛。
Eur J Pharmacol. 2012 May 5;682(1-3):79-85. doi: 10.1016/j.ejphar.2012.02.017. Epub 2012 Feb 21.
6
Isoform diversity and regulation in peripheral and central neurons revealed through RNA-Seq.通过 RNA-Seq 揭示外周和中枢神经元中的异构体多样性和调控。
PLoS One. 2012;7(1):e30417. doi: 10.1371/journal.pone.0030417. Epub 2012 Jan 17.
7
The dose can make the poison: lessons learned from adverse in vivo toxicities caused by RNAi overexpression.剂量决定毒性：从RNA干扰过表达引起的体内不良毒性中吸取的教训。
Silence. 2011 Oct 26;2:8. doi: 10.1186/1758-907X-2-8.
8
Lentivirus-siNgR199 promotes axonal regeneration and functional recovery in rats.慢病毒-siNgR199 促进大鼠轴突再生和功能恢复。
Int J Neurosci. 2012 Mar;122(3):133-9. doi: 10.3109/00207454.2011.633720. Epub 2011 Nov 29.
9
miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT.miRNA 介导的去腺苷酸化是由 GW182 通过与 CCR4-NOT 相互作用的两个保守基序来协调的。
Nat Struct Mol Biol. 2011 Oct 7;18(11):1211-7. doi: 10.1038/nsmb.2149.
10
miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs.miRNA 抑制涉及通过保守的 W 结构域结合基序介导的 GW182 募集 CCR4-NOT。
Nat Struct Mol Biol. 2011 Oct 7;18(11):1218-26. doi: 10.1038/nsmb.2166.
Zotero 插件