Introduction of 2,6-Diaminopurines into Serinol Nucleic Acid Improves Anti-miRNA Performance
Introduction of 2,6-Diaminopurines into Serinol Nucleic Acid Improves Anti-miRNA Performance
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DOI：
10.1002/cbic.201700272
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发表时间：
2017-10-05
期刊：
影响因子：
3.2
通讯作者：
Asanuma, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kamiya, Yukiko;Donoshita, Yuka;Asanuma, Hiroyuki
MicroRNAs(MiRNAs)是一种内源性小RNA，通过序列特异性杂交在转录后水平调节基因表达。抗miRNA寡核苷酸(AMOS)是miRNA活性的抑制剂。为了提高血清和细胞的结合亲和力和稳定性，需要对AMOS进行化学修饰。在这项研究中，我们以我们原来的无环核酸丝氨醇核酸(SNA)为骨架，以人工碱基2，6-二氨基嘌呤为原料合成了AMOS。仅由SNA组成的AMO具有很强的核酸酶抗性，并抑制了内源miRNA的活性。通过在SNA主链中引入2，6-二氨基嘌呤残基，AMO的抗miRNA活性显著提高。此外，我们还发现AMO活性的增强依赖于2，6-二氨基嘌呤残基在序列中的位置。SNA-AMOS的高效价表明，这些寡聚体将作为治疗试剂用于控制患者的miRNA功能，并作为研究microRNAs在细胞中的作用的工具。
MicroRNAs (miRNAs) are endogenous small RNAs that regulate gene expression at the post-transcriptional level by sequence-specific hybridisation. Anti-miRNA oligonucleotides (AMOs) are inhibitors of miRNA activity. Chemical modification of AMOs is required to increase binding affinity and stability in serum and cells. In this study, we synthesised AMOs with our original acyclic nucleic acid, serinol nucleic acid (SNA), backbone and with the artificial nucleobase 2,6-diaminopurine. The AMO composed of only SNA had strong nuclease resistance and blocked endogenous miRNA activity. A significant improvement in anti-miRNA activity of the AMO was achieved by introduction of a 2,6-diaminopurine residues into the SNA backbone. In addition, we found that the enhancement in AMO activity depended on the position of the 2,6-diaminopurine residue in the sequence. The high potency of the SNA-AMOs suggests that these oligomers will be useful as therapeutic reagents for control of miRNA function in patients and as tools for investigating the roles of microRNAs in cells.