Wang Leo L, Burdick Jason A
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Adv Healthc Mater. 2017 Jan;6(1). doi: 10.1002/adhm.201601041. Epub 2016 Dec 15.
It has been nearly two decades since RNA-interference (RNAi) was first reported. While there are no approved clinical uses, several phase II and III clinical trials suggest the great promise of RNAi therapeutics. One challenge for RNAi therapies is the controlled localization and sustained presentation to target tissues, to both overcome systemic toxicity concerns and to enhance in vivo efficacy. One approach that is emerging to address these limitations is the entrapment of RNAi molecules within hydrogels for local and sustained release. In these systems, nucleic acids are either delivered as siRNA conjugates or within nanoparticles. A plethora of hydrogels has been implemented using these approaches, including both traditional hydrogels that have already been developed for other applications and new hydrogels developed specifically for RNAi delivery. These hydrogels have been applied to various applications in vivo, including cancer, bone regeneration, inflammation and cardiac repair. This review will examine the design and implementation of such hydrogel RNAi systems and will cover the most recent applications of these systems.
自RNA干扰（RNAi）首次被报道以来，已经过去了近二十年。虽然目前尚无获批的临床应用，但多项II期和III期临床试验显示了RNAi疗法的巨大潜力。RNAi疗法面临的一个挑战是如何实现可控的定位并持续作用于靶组织，以克服对全身毒性的担忧并提高体内疗效。一种正在兴起的解决这些局限性的方法是将RNAi分子包裹在水凝胶中以实现局部和持续释放。在这些系统中，核酸要么作为siRNA缀合物递送，要么包裹在纳米颗粒内。已经使用这些方法实现了大量水凝胶，包括已经为其他应用开发的传统水凝胶以及专门为RNAi递送而开发的新型水凝胶。这些水凝胶已被应用于体内的各种应用，包括癌症、骨再生、炎症和心脏修复。本综述将研究此类水凝胶RNAi系统的设计与应用，并涵盖这些系统的最新应用。
