Ractigen Therapeutics, Nantong, China.
Department of Urology, Wuhan General Hospital, Guangzhou Command PLA, Wuhan, China.
Adv Exp Med Biol. 2017;983:217-229. doi: 10.1007/978-981-10-4310-9_16.
Small activating RNAs (saRNAs) are a class of artificially designed short duplex RNAs targeted at the promoter of a particular gene to upregulate its expression via a mechanism known as RNA activation (RNAa) and hold great promise for treating a wide variety of diseases including those undruggable by conventional therapies. The therapeutic benefits of saRNAs have been demonstrated in a number of preclinical studies carried out in different disease models including cancer. With many tumor suppressor genes (TSGs) downregulated due to either epigenetic mechanisms or haploinsufficiency resulting from deletion/mutation, cancer is an ideal disease space for saRNA therapeutics which can restore the expression of TSGs via epigenetic reprogramming. The p21 gene is a TSG frequently downregulated in cancer and an saRNA for p21 known as dsP21-322 has been identified to be a sequence-specific p21 activator in a number of cancer types. In this chapter, we review preclinical development of medicinal dsP21-322 for cancer, especially prostate cancer and bladder cancer, and highlight its potential for further clinical development.
小激活 RNA（saRNA）是一类人工设计的短双链 RNA，靶向特定基因的启动子，通过 RNA 激活（RNAa）机制上调其表达，为治疗多种疾病提供了巨大的潜力，包括传统疗法无法治疗的疾病。saRNA 在多种疾病模型（包括癌症）的临床前研究中已经证明了其治疗益处。由于表观遗传机制或缺失/突变导致的单倍不足，许多肿瘤抑制基因（TSG）下调，因此 saRNA 疗法是一种理想的治疗方法，它可以通过表观遗传重编程恢复 TSG 的表达。p21 基因是一种在癌症中经常下调的 TSG，一种名为 dsP21-322 的 p21 saRNA 已被确定为多种癌症类型中 p21 的序列特异性激活剂。在本章中，我们回顾了用于癌症（特别是前列腺癌和膀胱癌）的药用 dsP21-322 的临床前开发，并强调了其进一步临床开发的潜力。
