Antitumoral RNA-targeted oligonucleotide therapeutics: The third pillar after small molecule inhibitors and antibodies.
Antitumoral RNA-targeted oligonucleotide therapeutics: The third pillar after small molecule inhibitors and antibodies.
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DOI：
10.1111/cas.15461
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发表时间：
2022-09
期刊：
影响因子：
5.7
通讯作者：
Adachi, Yasushi
中科院分区：
文献类型：
--
作者：
Taniguchi, Hiroaki;Suzuki, Yasunori;Imai, Kohzoh;Adachi, Yasushi
关键词：
寡核苷酸治疗剂，由10-50个核苷酸长的单链或双链DNA或RNA分子组成的药物，可以结合特定的DNA或RNA序列或蛋白质，包括反义寡核苷酸（ASO），小干扰RNA（siRNA），microRNA（miRNA），适体和诱饵。这些寡核苷酸疗法可能成为药物开发的第三大支柱。特别是，AS 0和siRNA是广泛用于沉默基因表达的先进工具。它们用于临床试验，因为它们对靶mRNA和非编码RNA具有高度特异性，并且毒性有限。然而，其临床应用仍然具有挑战性。虽然化疗有好处，但它对许多患者有严重的副作用。因此，需要针对肿瘤的靶向分子治疗的新模式，包括寡核苷酸治疗，并且它们应该与使用下一代测序的诊断兼容。本文综述了反义寡核苷酸、siRNA和miRNA在恶性肿瘤临床研究中的应用。了解以前的研究和开发将有助于开发新的寡核苷酸治疗恶性肿瘤。反义寡核苷酸（ASO）和小干扰RNA（siRNA）是广泛使用的沉默基因表达的先进工具，甚至适用于通过其他治疗方式不可药物化的靶标。然而，由于脱靶效应，以及在靶部位和细胞中的累积较差，其在临床研究中的应用受到限制。寡核苷酸的药物递送系统（DDS）在克服这些困难方面发挥重要作用。
Oligonucleotide therapeutics, drugs consisting of 10–50 nucleotide‐long single‐ or double‐stranded DNA or RNA molecules that can bind to specific DNA or RNA sequences or proteins, include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamers, and decoys. These oligonucleotide therapeutics could potentially become the third pillar of drug development. In particular, ASOs and siRNAs are advanced tools that are widely used to silence gene expression. They are used in clinical trials, as they have high specificity for target mRNAs and non‐coding RNAs and limited toxicity. However, their clinical application remains challenging. Although chemotherapy has benefits, it has severe adverse effects in many patients. Therefore, new modalities for targeted molecular therapy against tumors, including oligonucleotide therapeutics, are required, and they should be compatible with diagnosis using next‐generation sequencing. This review provides an overview of the therapeutic uses of ASOs, siRNAs, and miRNAs in clinical studies on malignant tumors. Understanding previous research and development will help in developing novel oligonucleotide therapeutics against malignant tumors. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are widely‐used advanced tools for silencing gene expression, and even suitable for targets that are not druggable via other therapeutic modalities. However, their application in clinical studies is limited because of the off‐target effects, and poor accumulation at their target sites and cells. Drug delivery systems (DDSs) for oligonucleotides play an important role in overcoming these difficulties.
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