Pottash Alex Eli, Kuffner Christopher, Noonan-Shueh Madeleine, Jay Steven M
1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742 USA.
2Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 USA.
J Biol Eng. 2019 Feb 26;13:19. doi: 10.1186/s13036-018-0130-7. eCollection 2019.
Broad translational success of RNA interference (RNAi) technology depends on the development of effective delivery approaches. To that end, researchers have developed a variety of strategies, including chemical modification of RNA, viral and non-viral transfection approaches, and incorporation with delivery vehicles such as polymer- and lipid-based nanoparticles, engineered and native proteins, extracellular vesicles (EVs), and others. Among these, EVs and protein-based vehicles stand out as biomimetically-inspired approaches, as both proteins (e.g. Apolipoprotein A-1, Argonaute 2, and Arc) and EVs mediate intercellular RNA transfer physiologically. Proteins specifically offer significant therapeutic potential due to their biophysical and biochemical properties as well as their ability to facilitate and tolerate manipulation; these characteristics have made proteins highly successful translational therapeutic molecules in the last two decades. This review covers engineered protein vehicles for RNAi delivery along with what is currently known about naturally-occurring extracellular RNA carriers towards uncovering design rules that will inform future engineering of protein-based vehicles.
RNA干扰（RNAi）技术广泛的转化成功取决于有效递送方法的开发。为此，研究人员已经开发了多种策略，包括RNA的化学修饰、病毒和非病毒转染方法，以及与递送载体结合，如基于聚合物和脂质的纳米颗粒、工程蛋白和天然蛋白、细胞外囊泡（EVs）等。其中，EVs和基于蛋白质的载体作为仿生方法脱颖而出，因为蛋白质（如载脂蛋白A-1、Argonaute 2和Arc）和EVs在生理上都介导细胞间RNA转移。由于蛋白质的生物物理和生化特性以及它们促进和耐受操作的能力，蛋白质特别具有显著的治疗潜力；在过去二十年中，这些特性使蛋白质成为非常成功的转化治疗分子。本综述涵盖了用于RNAi递送的工程蛋白载体，以及目前对天然存在的细胞外RNA载体的了解，以揭示将为未来基于蛋白质的载体工程提供信息的设计规则。
