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反义寡核苷酸的可控递送:当前策略简要综述

Controlled delivery of antisense oligonucleotides: a brief review of current strategies.

作者信息

Zhao Xiubo, Pan Fang, Holt Cathy M, Lewis Andrew L, Lu Jian R

机构信息

University of Manchester, School of Physics and Astronomy, Biological Physics Group, Schuster Building, Manchester M13 9PL, UK.

出版信息

Expert Opin Drug Deliv. 2009 Jul;6(7):673-86. doi: 10.1517/17425240902992894.


DOI:10.1517/17425240902992894
PMID:19552611
Abstract

Antisense therapy has been investigated extensively over the past two decades, either experimentally for gene functional research or clinically as therapeutic agents owing to the conceptual simplicity, ease of design and low cost. The concept of this therapeutic approach is promising because short antisense oligonucleotides (ASOs) can be delivered into target cells for specific hybridisation with target mRNA, resulting in the inhibition of the expression of pathogenic genes. However, the efficient delivery of the ASO molecules into target cells remains challenging; this bottleneck together with several other technical hurdles need to be overcome before this approach becomes effective and widely adopted. A variety of vectors such as lipids, polymers, peptides and nanoparticles have been explored. This review outlines the recent advances of the non-viral ASO delivery strategies. Several recent scientific studies, including authors' contributions, have been selected to highlight the technical aspects of ASO delivery.

摘要

在过去二十年中,反义疗法得到了广泛研究,因其概念简单、易于设计且成本低廉,它既被用于基因功能研究的实验,也被用作临床治疗药物。这种治疗方法的概念很有前景,因为短反义寡核苷酸(ASO)可以被递送至靶细胞,与靶mRNA进行特异性杂交,从而抑制致病基因的表达。然而,将ASO分子有效递送至靶细胞仍然具有挑战性;在这种方法变得有效并被广泛采用之前,需要克服这一瓶颈以及其他几个技术障碍。人们已经探索了多种载体,如脂质、聚合物、肽和纳米颗粒。本综述概述了非病毒ASO递送策略的最新进展。我们选择了几项近期的科学研究,包括作者的贡献,以突出ASO递送的技术方面。

相似文献

[1]
Controlled delivery of antisense oligonucleotides: a brief review of current strategies.

Expert Opin Drug Deliv. 2009-7

[2]
Factors determining the efficacy of nuclear delivery of antisense oligonucleotides by gold nanoparticles.

Bioconjug Chem. 2008-5

[3]
A novel integrated strategy (full length gene targeting) for mRNA accessible site tagging combined with microarray hybridization/RNase H cleavage to screen effective antisense oligonucleotides.

Mol Vis. 2006-11-13

[4]
Reduction of liver tumor necrosis factor-alpha expression by targeting delivery of antisense oligonucleotides into Kupffer cells protects rats from fulminant hepatitis.

J Gene Med. 2009-3

[5]
Non-viral ocular gene therapy: potential ocular therapeutic avenues.

Adv Drug Deliv Rev. 2006-11-15

[6]
Antisense oligonucleotides: from design to therapeutic application.

Clin Exp Pharmacol Physiol. 2006

[7]
Oral delivery of siRNA and antisense oligonucleotides.

J Drug Target. 2009-8

[8]
Recent development of nonviral gene delivery systems with virus-like structures and mechanisms.

Eur J Pharm Biopharm. 2009-3

[9]
Polymer nanocarriers for the delivery of small fragments of nucleic acids: oligonucleotides and siRNA.

Eur J Pharm Biopharm. 2009-3

[10]
Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

Biomaterials. 2008

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