Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs.
Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs.
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DOI：
10.1093/nar/gkx1239
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发表时间：
2018-02-28
影响因子：
14.9
通讯作者：
Corey DR
中科院分区：
文献类型：
--
作者：
Shen X;Corey DR
RNA在所有基因的表达中起着核心作用。由于RNA内的任何序列都可以通过互补碱基配对识别，因此合成寡核苷酸和寡核苷酸模拟物提供了控制影响疾病的过程的一般策略。通过识别细胞RNA来调节表达的两种主要反义方法是单链反义寡核苷酸和双链体RNA。本文将讨论使合成核酸药物成为可能的化学修饰和分子机制。从最近的临床试验中吸取的经验教训将被总结。正在进行的临床试验可能会决定性地测试我们当前一代反义核酸技术的充分性，并突出需要更多基础研究的领域。
RNA plays a central role in the expression of all genes. Because any sequence within RNA can be recognized by complementary base pairing, synthetic oligonucleotides and oligonucleotide mimics offer a general strategy for controlling processes that affect disease. The two primary antisense approaches for regulating expression through recognition of cellular RNAs are single-stranded antisense oligonucleotides and duplex RNAs. This review will discuss the chemical modifications and molecular mechanisms that make synthetic nucleic acid drugs possible. Lessons learned from recent clinical trials will be summarized. Ongoing clinical trials are likely to decisively test the adequacy of our current generation of antisense nucleic acid technologies and highlight areas where more basic research is needed.