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采用可逆加成-断裂链转移聚合合成的 ABA 三嵌段共聚物递送的 siRNA 在体内抑制流感病毒。

Inhibition of influenza virus in vivo by siRNA delivered using ABA triblock copolymer synthesized by reversible addition-fragmentation chain-transfer polymerization.

机构信息

The Commonwealth Scientific & Industrial Research Organisation, Animal, Food & Health Sciences, Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC 3220, Australia.

出版信息

Nanomedicine (Lond). 2014;9(8):1141-54. doi: 10.2217/nnm.13.119. Epub 2013 Dec 23.

Abstract

AIM

Influenza virus remains a major threat, with outbreaks continuing to occur. Few treatment options are available and drug resistance can emerge rapidly. New drugs that can quickly be adapted to virus mutations are needed. Several highly effective siRNAs targeting influenza that inhibit virus replication are known; however, effective delivery of these siRNAs remains a challenge. The aim of this study was to demonstrate the safety and efficacy of ABA triblock copolymer-delivered siRNA to inhibit influenza virus replication in vivo.

MATERIALS & METHODS: We report on the delivery of a siRNA targeting the influenza virus in chicken embryos using an ABA triblock copolymer prepared by reversible addition-fragmentation chain-transfer polymerization, containing a central cationic block and two outer hydrophilic polyethylene glycol blocks.

RESULTS

A significant reduction of virus titer was observed with the polymer/anti-influenza siRNA complexes, whereas the control with polymer/control siRNA complexes showed no effect.

CONCLUSION

These data suggest that a reversible addition-fragmentation chain transfer-based siRNA delivery platform may be suitable for combating infectious diseases in vivo.

摘要

目的

流感病毒仍然是一个主要威胁,其爆发仍在继续。目前可用的治疗方法有限,而且药物耐药性可能迅速出现。需要能够快速适应病毒突变的新药。已经有几种针对流感的高效 siRNA 可以抑制病毒复制;然而,这些 siRNA 的有效传递仍然是一个挑战。本研究旨在证明 ABA 三嵌段共聚物递送的 siRNA 抑制体内流感病毒复制的安全性和有效性。

材料与方法

我们报告了使用通过可逆加成-断裂链转移聚合制备的 ABA 三嵌段共聚物在鸡胚中递送靶向流感病毒的 siRNA 的情况,该共聚物包含一个中心阳离子嵌段和两个外部亲水性聚乙二醇嵌段。

结果

与聚合物/对照 siRNA 复合物相比,观察到聚合物/抗流感 siRNA 复合物的病毒滴度显著降低,而聚合物/对照 siRNA 复合物则没有效果。

结论

这些数据表明,基于可逆加成-断裂链转移的 siRNA 传递平台可能适用于体内对抗传染病。

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