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Open AccessArticle

Development of Novel antimiRzymes for Targeted Inhibition of miR-21 Expression in Solid Cancer Cells

1,†, 1,2,† and 1,2,*
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA 6150, Australia
Perron Institute for Neurological and Translational Science, Perth, WA 6009, Australia
Author to whom correspondence should be addressed.
These authors contributed equally.
Molecules 2019, 24(13), 2489;
Received: 12 June 2019 / Revised: 5 July 2019 / Accepted: 5 July 2019 / Published: 7 July 2019
(This article belongs to the Section Bioorganic Chemistry)
PDF [1126 KB, uploaded 7 July 2019]


MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the regulation of gene expression. Previous reports showed an over-expression of miRNA-21 (miR-21) in various cancer cells, and its up-regulation is closely related to cancer initiation, proliferation and metastasis. In this work, we envisioned the development of novel antimiRzymes (anti-miRNA-DNAzyme) that are capable of selectively targeting and cleaving miR-21 and inhibit its expression in cancer cells using the DNAzyme technique. For this purpose, we have designed different antimiRzyme candidates by systematically targeting different regions of miR-21. Our results demonstrated that RNV541, a potential arm-loop-arm type antimiRzyme, was very efficient (90%) to suppress miR-21 expression in U87MG malignant glioblastoma cell line at 200 nM concentration. In addition, RNV541 also inhibited miR-21 expression (50%) in MDA-MB-231 breast cancer cell line. For targeted delivery, we conjugated RNV541 with a transferrin receptor (TfR) targeting aptamer for TfR-mediated cancer cell delivery. As expected, the developed chimeric structure efficiently delivered the antimiRzyme RNV541 into TfR positive glioblastoma cells. TfR aptamer-RNV541 chimeric construct showed 52% inhibition of miR-21 expression in U87MG glioblastoma cells at 2000 nM concentration, without using any transfection reagents, making it a highly desirable strategy to tackle miR-21 over-expressed malignant cancers. Although these are in vitro based observations, based on our results, we firmly believe that our findings could be beneficial towards the development of targeted cancer therapeutics where conventional therapies face several challenges. View Full-Text
Keywords: oligonucleotides; DNAzyme; antimiRzyme; miR-21 targeting oligonucleotides; DNAzyme; antimiRzyme; miR-21 targeting

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Larcher, L.M.; Wang, T.; Veedu, R.N. Development of Novel antimiRzymes for Targeted Inhibition of miR-21 Expression in Solid Cancer Cells. Molecules 2019, 24, 2489.

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