Coan Michela, Haefliger Simon, Ounzain Samir, Johnson Rory
School of Biology and Environmental Science, University College Dublin, Dublin, Ireland.
Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Dublin, Ireland.
Nat Rev Genet. 2024 Aug;25(8):578-595. doi: 10.1038/s41576-024-00693-2. Epub 2024 Feb 29.
RNA therapeutics (RNATx) aim to treat diseases, including cancer, by targeting or employing RNA molecules for therapeutic purposes. Amongst the most promising targets are long non-coding RNAs (lncRNAs), which regulate oncogenic molecular networks in a cell type-restricted manner. lncRNAs are distinct from protein-coding genes in important ways that increase their therapeutic potential yet also present hurdles to conventional clinical development. Advances in genome editing, oligonucleotide chemistry, multi-omics and RNA engineering are paving the way for efficient and cost-effective lncRNA-focused drug discovery pipelines. In this Review, we present the emerging field of lncRNA therapeutics for oncology, with emphasis on the unique strengths and challenges of lncRNAs within the broader RNATx framework. We outline the necessary steps for lncRNA therapeutics to deliver effective, durable, tolerable and personalized treatments for cancer.
RNA疗法（RNATx）旨在通过靶向或利用RNA分子用于治疗目的来治疗包括癌症在内的疾病。最有前景的靶点之一是长链非编码RNA（lncRNA），它以细胞类型受限的方式调节致癌分子网络。lncRNA在重要方面与蛋白质编码基因不同，这增加了它们的治疗潜力，但也给传统临床开发带来了障碍。基因组编辑、寡核苷酸化学、多组学和RNA工程方面的进展正在为高效且经济高效的以lncRNA为重点的药物发现管道铺平道路。在本综述中，我们介绍了肿瘤学中lncRNA疗法的新兴领域，重点关注lncRNA在更广泛的RNATx框架内的独特优势和挑战。我们概述了lncRNA疗法为癌症提供有效、持久、可耐受和个性化治疗所需的步骤。
