Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.
Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.
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内体贩运机械的化学操纵：对寡核苷酸递送的影响。
DOI：
10.3390/biomedicines9050512
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发表时间：
2021-05-05
期刊：
影响因子：
4.7
通讯作者：
Juliano RL
中科院分区：
文献类型：
--
作者：
Juliano RL
反义寡核苷酸(ASO)、siRNA和剪接开关寡核苷酸(SSO)都具有巨大的治疗潜力，随着寡核苷酸进入临床，这种潜力正在得到验证。然而，基于寡核苷酸的疗法的进展一直受到限制，因为难以将这些复杂分子运送到它们在特定组织中的细胞质或细胞核中的作用部位。交付问题有两个方面。首先，大多数类型的寡核苷酸在非肝脏组织中的摄取率很低。第二，被细胞摄取的大部分寡核苷酸被困在内体中，在那里它是药理上不活跃的。越来越多的人认识到，内体捕获是寡核苷酸治疗的一个关键制约因素。因此，已经设计了许多方法来解决这个问题，主要是基于各种纳米颗粒技术的方法。然而，最近出现了一种替代方法，它使用小分子来操纵细胞内的转运过程，以增强寡核苷酸的作用。本文综述了这种化学生物学方法在寡核苷酸递送方面的研究现状，并试图指出未来发展的可能途径。
Antisense oligonucleotides (ASOs), siRNA and splice switching oligonucleotides (SSOs) all have immense potential as therapeutic agents, potential that is now being validated as oligonucleotides enter the clinic. However, progress in oligonucleotide-based therapeutics has been limited by the difficulty in delivering these complex molecules to their sites of action in the cytosol or nucleus of cells within specific tissues. There are two aspects to the delivery problem. The first is that most types of oligonucleotides have poor uptake into non-hepatic tissues. The second is that much of the oligonucleotide that is taken up by cells is entrapped in endosomes where it is pharmacologically inert. It has become increasingly recognized that endosomal trapping is a key constraint on oligonucleotide therapeutics. Thus, many approaches have been devised to address this problem, primarily ones based on various nanoparticle technologies. However, recently an alternative approach has emerged that employs small molecules to manipulate intracellular trafficking processes so as to enhance oligonucleotide actions. This review presents the current status of this chemical biology approach to oligonucleotide delivery and seeks to point out possible paths for future development.
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DOI：
10.3390/molecules22060891
发表时间：
2017-05-27
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chen C;Lu Y;Siu HM;Guan J;Zhu L;Zhang S;Yue J;Zhang L
通讯作者：
Zhang L
影响因子：
4.7
作者：
Alam, Md Rowshon;Ming, Xin;Fisher, Michael;Lackey, Jeremy G.;Rajeev, Kallanthottathil G.;Manoharan, Muthiah;Juliano, Rudy L.
通讯作者：
Juliano, Rudy L.
影响因子：
6
作者：
Daussy CF;Wodrich H
通讯作者：
Wodrich H
DOI：
10.1111/j.1600-0854.2009.00915.x
发表时间：
2009-07
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
de Lartigue J;Polson H;Feldman M;Shokat K;Tooze SA;Urbé S;Clague MJ
通讯作者：
Clague MJ
影响因子：
46.9
作者：
Gilleron, Jerome;Querbes, William;Zerial, Marino
通讯作者：
Zerial, Marino