Non-coding RNAs (ncRNAs) like microRNAs (miRNAs) or small interference RNAs (siRNAs) with their power to selectively silence any gene of interest enable the targeting of so far 'undruggable' proteins and diseases. Such RNA molecules have gained much attention from biotech and pharmaceutical companies, which led to the first Food and Drug Administration (FDA) approved ncRNA therapeutic in 2018. However, the main barrier in clinical practice of ncRNAs is the lack of an effective delivery system that can protect the RNA molecules from nuclease degradation, deliver them to specific tissues and cell types, and release them into the cytoplasm of the targeted cells, all without inducing adverse effects. For that reason, drug delivery approaches, formulations, technologies and systems for transporting pharmacological ncRNA compounds to achieve a diagnostic or therapeutic effect in the human body are in demand. Here, we review the development of therapeutic lipid-based nanoparticles for delivery of miRNAs, one class of endogenous ncRNAs with specific regulatory functions. We outline challenges and opportunities for advanced miRNA-based therapies, and discuss the complexity associated with the delivery of functional miRNAs. Novel strategies are addressed how to deal with the most critical points in miRNA delivery, such as toxicity, specific targeting of disease sites, proper cellular uptake and endosomal escape of miRNAs. Current fields of application and various preclinical settings involving miRNA therapeutics are discussed, providing an outlook to future clinical approaches. Following the current trends and technological developments in nanomedicine exciting new delivery systems for ncRNA-based therapeutics can be expected in upcoming years.

中文翻译：

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用于microRNA输送的脂质纳米载体。

诸如microRNA（miRNA）或小型干扰RNA（siRNA）之类的非编码RNA（ncRNA）具有选择性沉默任何目的基因的能力，因此可以靶向目前“不可负担的”蛋白质和疾病。此类RNA分子引起了生物技术公司和制药公司的广泛关注，这导致食品和药物管理局（FDA）在2018年首次批准了ncRNA治疗剂。然而，ncRNAs在临床实践中的主要障碍是缺乏有效的递送系统。可以保护RNA分子免于核酸酶降解，将其传递到特定的组织和细胞类型，并将其释放到目标细胞的细胞质中，而不会引起不利影响。因此，药物输送方法，配方，需要用于转运药理学ncRNA化合物以在人体中实现诊断或治疗效果的技术和系统。在这里，我们回顾了基于治疗​​脂质的纳米颗粒用于miRNA的发展，miRNA是一类具有特定调控功能的内源性ncRNA。我们概述了基于miRNA的高级疗法的挑战和机遇，并讨论了与功能性miRNA的递送相关的复杂性。解决新策略的方法是如何应对miRNA传递中的最关键点，例如毒性，特定的疾病部位靶向，适当的细胞摄取和miRNA的内体逃逸。讨论了涉及miRNA治疗剂的当前应用领域和各种临床前设置，为未来的临床方法提供了前景。