Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, CA, USA.
Methods Mol Biol. 2022;2521:191-206. doi: 10.1007/978-1-0716-2441-8_10.
Therapeutic RNAs, such as antisense oligonucleotides (ASOs), aptamers, small-interfering RNAs (siRNAs), microRNAs (miRs or miRNAs), messenger RNAs (mRNAs), and guide RNAs (gRNAs), represent a novel class of modalities that not only increase the molecular diversity of medications but also expand the range of druggable targets. To develop noncoding RNA therapeutics for the treatment of cancer diseases, we have established a novel robust RNA bioengineering platform to achieve high-yield and large-scale production of true biologic RNA agents, which are proven to be functional in the control of target gene expression and effective in the management of tumor progression in various models. Herein, we describe the methods for bioengineered RNA (BioRNA or BERA) therapy in patient-derived organoids (PDOs) in vitro and patient-derived xenograft (PDX) mouse models in vivo. The efficacy of a BioRNA, miR-1291, in the inhibition of pancreatic cancer PDO and PDX growth is exemplified in this chapter.
治疗性 RNA，如反义寡核苷酸 (ASO)、适体、小干扰 RNA (siRNA)、microRNA (miR 或 miRNAs)、信使 RNA (mRNA) 和引导 RNA (gRNA)，代表了一类新型的治疗方式，不仅增加了药物的分子多样性，还扩展了可药物治疗靶点的范围。为了开发用于癌症治疗的非编码 RNA 疗法，我们建立了一种新型的强大的 RNA 生物工程平台，以实现高产和大规模生产真正的生物 RNA 药物，这些药物已被证明在控制靶基因表达和有效管理各种模型中的肿瘤进展方面具有功能。在此，我们描述了在体外患者来源的类器官 (PDO) 和体内患者来源的异种移植 (PDX) 小鼠模型中进行生物工程 RNA (BioRNA 或 BERA) 治疗的方法。本文以 miR-1291 抑制胰腺癌细胞 PDO 和 PDX 生长为例说明了 BioRNA 的疗效。
