CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Oncode Institute, Hubrecht Institute-KNAW and University Medical Center, Uppsalalaan 8, 3584 CT Utrecht, Utrecht, the Netherlands.
Adv Drug Deliv Rev. 2021 Jul;174:250-264. doi: 10.1016/j.addr.2021.04.017. Epub 2021 Apr 21.
RNA-based therapeutics are highly promising for the treatment of numerous diseases, by their ability to tackle the genetic origin in multiple possible ways. RNA molecules are, however, incapable of crossing cell membranes, hence a safe and efficient delivery vehicle is pivotal. Extracellular vesicles (EVs) are endogenously derived nano-sized particles and possess several characteristics which make them excellent candidates as therapeutic RNA delivery agent. This includes the inherent capability to functionally transfer RNAs in a selective manner and an enhanced safety profile compared to synthetic particles. Nonetheless, the fundamental mechanisms underlying this selective inter- and intracellular trafficking and functional transfer of RNAs by EVs are poorly understood. Improving our understanding of these systems is a key element of working towards an EV-based or EV-mimicking system for the functional delivery of therapeutic RNA. In this review, state-of-the-art approaches to detect and visualize RNA in situ and in live cells are discussed, as well as strategies to assess functional RNA transfer, highlighting their potential in studying EV-RNA trafficking mechanisms.
基于 RNA 的疗法具有通过多种可能的方式解决遗传起源的能力，因此非常有希望用于治疗多种疾病。然而，RNA 分子无法穿过细胞膜，因此安全有效的递送载体至关重要。细胞外囊泡 (EV) 是内源性衍生的纳米级颗粒，具有使其成为治疗性 RNA 递药剂的理想候选物的多个特征。这包括以选择性方式功能转移 RNA 的固有能力以及与合成颗粒相比增强的安全性。尽管如此，EV 介导的 RNA 选择性细胞间和细胞内转运和功能转移的基本机制仍知之甚少。深入了解这些系统是开发基于 EV 或 EV 模拟系统以实现治疗性 RNA 功能递送的关键因素。在这篇综述中，讨论了用于原位和活细胞中检测和可视化 RNA 的最新方法，以及评估功能性 RNA 转移的策略，突出了它们在研究 EV-RNA 转运机制中的潜力。
