Absolute quantification of mammalian microRNAs for therapeutic RNA cleavage and detargeting

MicroRNAs (miRNAs) are small regulatory RNAs that destabilize partially complementary transcripts and cleave perfectly paired targets. miRNAs are often expressed in a specific tissue, allowing miRNA-directed cleavage to be used to prevent genome editing or gene replacement therapy in unintended cell types, a strategy called detargeting. miRNA intracellular concentration influences the potency of gene silencing, yet the absolute steady-state levels of just a few miRNAs have been determined in mammalian tissues. Here, we report the absolute abundance of miRNAs in 14 human and mouse cell lines and 17 mouse tissues, including eight brain regions. Our experiments in human cultured cells demonstrate that both miRNA and target levels influence efficacy of cleavage of fully complementary transcripts. We report the miRNA concentration required for productive cleavage of highly expressed transcripts and identify mouse miRNAs that reach this threshold in vivo.

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Publication Details

Journal
RNA
Published
2025-05-28
DOI
https://doi.org/10.1261/rna.080566.125
Citations
2
Primary Topic
MicroRNA in disease regulation
Type
article
Field-Weighted Citation Impact
1.87

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article

Absolute quantification of mammalian microRNAs for therapeutic RNA cleavage and detargeting

Kathryn Chase, Mina Zamani, Erik J. Sontheimer, Wen Xue et al.
2 citations
RNA
MicroRNA in disease regulation
1.87
article

Absolute quantification of mammalian microRNAs for therapeutic RNA cleavage and detargeting

Kathryn Chase, Mina Zamani, Erik J. Sontheimer, Wen Xue, Shun‐Qing Liang, Katharine Cecchini, Jennifer A. Broderick, Haiying Zheng, Mengqi Yang, Carolyn Kraus, Olena Kolumba, Nandagopal Ajaykumar, Jooyoung Lee, Jiayi Wang
article en
2 citations

Abstract

MicroRNAs (miRNAs) are small regulatory RNAs that destabilize partially complementary transcripts and cleave perfectly paired targets. miRNAs are often expressed in a specific tissue, allowing miRNA-directed cleavage to be used to prevent genome editing or gene replacement therapy in unintended cell types, a strategy called detargeting. miRNA intracellular concentration influences the potency of gene silencing, yet the absolute steady-state levels of just a few miRNAs have been determined in mammalian tissues. Here, we report the absolute abundance of miRNAs in 14 human and mouse cell lines and 17 mouse tissues, including eight brain regions. Our experiments in human cultured cells demonstrate that both miRNA and target levels influence efficacy of cleavage of fully complementary transcripts. We report the miRNA concentration required for productive cleavage of highly expressed transcripts and identify mouse miRNAs that reach this threshold in vivo.

RNAVol. 31(8)
University of Minnesota (US), University of Massachusetts Chan Medical School (US), Twin Cities Orthopedics (US), New York University (US)
Zegar Family Foundation, National Institutes of Health
Openalex Percentile: Top 14%
MicroRNA in disease regulation
1.87
DOIOpen Access PDFOpenAlex
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