Precise protein expression through microRNA-mediated gene dosage compensation

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Skip to main contentTools of the TradePublished: 27 February 2026Rongrong Du  ORCID: orcid.org/0009-0003-4942-30201,2 Nature Reviews Molecular Cell Biology (2026)Cite this articleSubjectsmiRNAsSynthetic biologyTransgene expression in cells and organisms underpins much of modern biological research. However, most commonly used expression systems generate broad and poorly controlled distributions of protein levels, leading to inaccurate experimental results and, in some contexts, overexpression-associated toxicity. These limitations complicate both quantitative biology and therapeutic applications, for which precise control of protein dosage is essential.DIMMERs provide tuneable control of protein expression through modular design parameters, including the degree of miRNA–target complementarity, and miRNA copy number. An empirically derived miRNA design algorithm further extends the method from single-gene regulation to simultaneous regulation of multiple genes, thereby enabling the construction of defined protein expression ‘cocktails’ within the same cell. Importantly, DIMMERs are compatible with diverse cell types and delivery methods.This is a preview of subscription content, access via your institutionAccess optionsAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription27,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access269,00 € per yearonly 22,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to the full article PDF.39,95 €Prices may be subject to local taxes which are calculated during checkoutReferencesOriginal articleDu, R. et al. miRNA modules for precise, tunable control of gene expression. Mol. Cell 86, 194–212.e7 (2026)Article  CAS  PubMed  Google Scholar Download referencesAuthor informationAuthors and AffiliationsDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USARongrong DuHoward Hughes Medical Institute, California Institute of Technology, Pasadena, CA, USARongrong DuAuthorsRongrong DuView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Rongrong Du.Ethics declarationsRights and permissionsReprints and permissionsAbout this article