Many miRNA inhibitors have been developed, including chemically modified oligonucleotides, such as 2'-O-methylated RNA and locked nucleic acid (LNA). Unmodified DNA has not yet been reported as a miRNA inhibitor due to relatively low DNA/miRNA binding affinity. We designed a structured DNA, LidNA, which was constructed with unmodified DNA, consisting of a complementary sequence to the target miRNA flanked by two structured DNA regions, such as double-stranded DNA. LidNA inhibited miRNA activity more potently than 2'-O-methylated RNA or LNA. To optimize LidNA, two double-stranded regions were joined, causing the molecule to assume a delta-like shape, which we termed delta-type LidNA. Delta-type LidNAs were developed to target endogenous and exogenous miRNAs, and exhibited potent miRNA inhibitory effects with a duration of at least 10 days. Delta-type LidNA-21, which targeted miR-21, inhibited the growth of cancer cell lines. This newly developed LidNA could contribute to miRNA studies across multiple fields.Abbreviations: LidNA: DNA that puts a lid on miRNA function; LNA: locked nucleic acid; 3'-UTR: 3'-untranslated regions; RISC: RNA-induced silencing complex; MBL: Molecular beacon-like LidNA; YMBL: Y-type molecular beacon-like LidNA; TDMD: target-directed microRNA degradation.

中文翻译：

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LidNA的结构改进：δ型LidNA是用未修饰的DNA构建的有效miRNA抑制剂。

已经开发了许多miRNA抑制剂，包括化学修饰的寡核苷酸，例如2'-O-甲基化RNA和锁核酸（LNA）。由于相对较低的DNA / miRNA结合亲和力，未修饰的DNA尚未被报道为miRNA抑制剂。我们设计了一种结构化的DNA，即LidNA，该结构由未经修饰的DNA构成，该DNA由与目标miRNA互补的序列组成，两侧是两个结构化DNA区域（例如双链DNA）。LidNA比2'-O-甲基化RNA或LNA更有效地抑制miRNA活性。为了优化LidNA，将两个双链区连接起来，使分子呈现出类似delta的形状，我们称之为delta型LidNA。Delta型LidNAs被开发为靶向内源性和外源性miRNA，并在至少10天的时间里表现出有效的miRNA抑制作用。靶向miR-21的Delta型LidNA-21可抑制癌细胞系的生长。这项新开发的LidNA可能有助于跨多个领域的miRNA研究。LNA：锁核酸；3'-UTR：3'-非翻译区；RISC：RNA诱导的沉默复合物；MBL：分子信标样LidNA；YMBL：Y型分子信标状LidNA；TDMD：定向的microRNA降解。Y型分子信标样LidNA; TDMD：定向的microRNA降解。Y型分子信标样LidNA; TDMD：定向的microRNA降解。