Technologies for controlled, local delivery of siRNA.
Technologies for controlled, local delivery of siRNA.
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DOI：
10.1016/j.jconrel.2015.09.066
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发表时间：
2015-11-28
期刊：
影响因子：
--
通讯作者：
Duvall CL
中科院分区：
文献类型：
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作者：
Sarett SM;Nelson CE;Duvall CL
20世纪90年代末发现的RNAi开启了一个新的治疗可能性领域，理论上可以有效和特异性沉默任何所需的遗传靶标。更好地阐明作用机制，稳定和减少siRNA分子非特异性作用的化学修饰的影响，以及有效递送系统的关键设计考虑因素，推动了开发临床成功的siRNA疗法的进展。初始siRNA翻译的逻辑目标是局部治疗，因为将siRNA直接递送到其作用部位有助于确保足够的剂量到达靶组织，减少脱靶副作用的可能性，并绕过实质性的全身递送障碍。虽然局部siRNA递送已经进展到许多临床试验中，但是也存在巨大的机会来开发能够在空间和时间上控制基因沉默的持续释放的局部递送系统。这篇评论的重点是建立本地化和控制基因沉默的材料平台，重点是最有希望的临床翻译系统。
The discovery of RNAi in the late 1990s unlocked a new realm of therapeutic possibilities by enabling potent and specific silencing of theoretically any desired genetic target. Better elucidation of the mechanism of action, the impact of chemical modifications that stabilize and reduce nonspecific effects of siRNA molecules, and the key design considerations for effective delivery systems has spurred progress toward developing clinically-successful siRNA therapies. A logical aim for initial siRNA translation is local therapies, as delivering siRNA directly to its site of action helps to ensure that a sufficient dose reaches the target tissue, lessens the potential for off-target side effects, and circumvents the substantial systemic delivery barriers. While topical siRNA delivery has progressed into numerous clinical trials, an enormous opportunity also exists to develop sustained-release, local delivery systems that enable both spatial and temporal control of gene silencing. This review focuses on material platforms that establish both localized and controlled gene silencing, with emphasis on the systems that show most promise for clinical translation.