Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
Methods Mol Biol. 2020;2115:1-22. doi: 10.1007/978-1-0716-0290-4_1.
RNA interference (RNAi), a natural gene silencing process, is a widely used technique in basic research, preclinical studies, and drug development strategies. Although the technique has great potential to generate new human therapies and treat undruggable diseases, the clinical application of RNAi is still challenging primarily because of the delivery problem and potential off-target effects. Over the past two decades, great efforts have been undertaken to develop delivery agents and chemical modifications to overcome these challenges. Such advances in RNA delivery and chemical modifications have benefited researchers who are developing gene-editing therapies based on CRISPR-Cas9, an RNA-guided endonuclease, which is already having a major impact on biology and medicine. Here, I review the discovery of these two interference tools, identify the technical challenges yet to be overcome and provide some perspectives on how these two RNA-based technologies can be harnessed to treat human diseases.
RNA 干扰（RNAi）是一种天然的基因沉默过程，是基础研究、临床前研究和药物开发策略中广泛使用的技术。尽管该技术具有产生新的人类治疗方法和治疗无药可治疾病的巨大潜力，但 RNAi 的临床应用仍然具有挑战性，主要是因为递送问题和潜在的脱靶效应。在过去的二十年中，人们已经做出了巨大的努力来开发递送剂和化学修饰物来克服这些挑战。这些在 RNA 递送上的进展和化学修饰的改进使基于 CRISPR-Cas9 的基因编辑疗法的研究人员受益，CRISPR-Cas9 是一种 RNA 指导的内切酶，它已经对生物学和医学产生了重大影响。在这里，我回顾了这两种干扰工具的发现，确定了尚未克服的技术挑战，并就如何利用这两种基于 RNA 的技术来治疗人类疾病提供了一些观点。
