Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Nucleic Acids Res. 2010 Jul;38(13):4466-75. doi: 10.1093/nar/gkq160. Epub 2010 Mar 11.
MicroRNAs (miRNAs) play an important role in diverse physiological processes and are potential therapeutic agents. Synthetic oligonucleotides (ONs) of different chemistries have proven successful for blocking miRNA expression. However, their specificity and efficiency have not been fully evaluated. Here, we show that peptide nucleic acids (PNAs) efficiently block a key inducible miRNA expressed in the haematopoietic system, miR-155, in cultured B cells as well as in mice. Remarkably, miR-155 inhibition by PNA in primary B cells was achieved in the absence of any transfection agent. In mice, the high efficiency of the treatment was demonstrated by a strong overlap in global gene expression between B cells isolated from anti-miR-155 PNA-treated and miR-155-deficient mice. Interestingly, PNA also induced additional changes in gene expression. Our analysis provides a useful platform to aid the design of efficient and specific anti-miRNA ONs for in vivo use.
微小 RNA（miRNAs）在多种生理过程中发挥重要作用，是有潜力的治疗药物。不同化学性质的合成寡核苷酸（ONs）已被证明可成功阻断 miRNA 的表达。然而，它们的特异性和效率尚未得到充分评估。在这里，我们表明肽核酸（PNAs）可有效阻断造血系统中关键诱导型 miRNA，即 miR-155 的表达，不仅在体外培养的 B 细胞中，在体内小鼠中也如此。值得注意的是，在不存在任何转染试剂的情况下，PNA 即可在原代 B 细胞中实现 miR-155 的抑制。在小鼠中，从抗 miR-155 PNA 处理和 miR-155 缺失小鼠中分离的 B 细胞之间存在高度重叠的全局基因表达，这证明了该治疗方法的高效性。有趣的是，PNA 还诱导了其他基因表达的变化。我们的分析提供了一个有用的平台，有助于设计用于体内应用的高效和特异性抗 miRNA ONs。
