开发小激活RNA作为一种治疗手段：当前的挑战与前景

Developing small activating RNA as a therapeutic: current challenges and promises.

作者信息

Kwok Albert, Raulf Nina, Habib Nagy

机构信息

MiNA Therapeutics Limited, Translation & Innovation Hub, 80 Wood Lane, London W12 0BZ, UK.

Department of Surgery & Cancer, Hammersmith Hospital, Imperial College London, Du Cane Road, London W12 0NN, UK.

出版信息

Ther Deliv. 2019 Mar;10(3):151-164. doi: 10.4155/tde-2018-0061.

DOI:10.4155/tde-2018-0061

PMID:30909853

Abstract

RNA activation (RNAa) allows specific gene upregulation mediated by a small activating RNA (saRNA). Harnessing this process would help in developing novel therapeutics for undruggable diseases. Since its discovery in mid 2000s, improvements of saRNA design, synthetic chemistry and understanding of the biology have matured the way to apply RNAa. Indeed, MiNA therapeutics Ltd has conducted the first RNAa clinical trial for advanced hepatocellular carcinoma patients with promising outcomes. However, to fully realize the RNAa potential better saRNA delivery strategies are needed to target other diseases. Currently, saRNA can be delivered in vivo by lipid nanoparticles, dendrimers, lipid and polymer hybrids and aptamers. Further developing these delivery technologies and novel application of RNAa will prove to be invaluable for new treatment development.

摘要

RNA激活（RNAa）可实现由小激活RNA（saRNA）介导的特定基因上调。利用这一过程将有助于开发针对难以成药疾病的新型疗法。自21世纪中叶发现以来，saRNA设计、合成化学以及对生物学的理解等方面的改进，使RNAa的应用方式更加成熟。事实上，MiNA Therapeutics有限公司已针对晚期肝细胞癌患者开展了首例RNAa临床试验，结果令人鼓舞。然而，为了充分实现RNAa的潜力，需要更好的saRNA递送策略来针对其他疾病。目前，saRNA可通过脂质纳米颗粒、树枝状大分子、脂质与聚合物杂化物以及适体在体内递送。进一步开发这些递送技术以及RNAa的新应用对于新疗法的开发将具有不可估量的价值。