Self-modulating therapeutic platform using engineered miRNA-responsive oligonucleotides.

IF 13.4 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Doyeong Ku, Hansol Kim, JinA Lim, Jayeon Song, Junhyeok Yoon, Liu Jun, Su-Ji Min, Ryeongeun Cho, Namseok Lee, Kyunghoon Hur, Jong-Eun Park, Luke P Lee, Junshik Hong, Yoosik Kim, Hyun Gyu Park
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引用次数: 0

Abstract

Due to a pivotal role in the post-transcriptional regulation of genes implicated in numerous diseases, miRNAs serve as promising disease biomarkers and therapeutic targets. We introduce a new oligonucleotide probe termed miRNA-trigger, which selectively downregulates newly assigned target mRNAs by hijacking specific miRNAs. By engineering the miRNA-trigger to suppress the anti-apoptotic BCL-xL gene, we induce apoptosis selectively in breast cancer cells overexpressing specific miRNAs and further validate its therapeutic efficacy in vivo, by significantly reducing the tumor volume of the xenograft mouse upon its tail-vein injection. This approach establishes a new platform for self-modulating oligonucleotide therapy by redirecting disease-associated miRNAs.

使用工程化mirna反应性寡核苷酸的自调节治疗平台。
由于mirna在许多疾病相关基因的转录后调控中起着关键作用,因此mirna可作为有希望的疾病生物标志物和治疗靶点。我们引入了一种新的寡核苷酸探针,称为miRNA-trigger,它通过劫持特定的mirna,选择性地下调新分配的靶mrna。通过设计miRNA-trigger来抑制抗凋亡的BCL-xL基因,我们在过表达特定mirna的乳腺癌细胞中选择性诱导凋亡,并进一步验证其在体内的治疗效果,在其尾静脉注射后显著减少异种移植小鼠的肿瘤体积。这种方法通过重定向疾病相关的mirna,为自我调节寡核苷酸治疗建立了一个新的平台。
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来源期刊
Nano Convergence
Nano Convergence Engineering-General Engineering
CiteScore
15.90
自引率
2.60%
发文量
50
审稿时长
13 weeks
期刊介绍: Nano Convergence is an internationally recognized, peer-reviewed, and interdisciplinary journal designed to foster effective communication among scientists spanning diverse research areas closely aligned with nanoscience and nanotechnology. Dedicated to encouraging the convergence of technologies across the nano- to microscopic scale, the journal aims to unveil novel scientific domains and cultivate fresh research prospects. Operating on a single-blind peer-review system, Nano Convergence ensures transparency in the review process, with reviewers cognizant of authors' names and affiliations while maintaining anonymity in the feedback provided to authors.
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