Evidence map›Paper›PMID 41421338›Full record

ArticleMolecular cell2026

miRNA modules for precise, tunable control of gene expression.

Rongrong Du, Michael J Flynn, Karan Mahe, Monique Honsa, Bo Gu, Dongyang Li, Sean E McGeary, Viviana Gradinaru, Ralf Jungmann, Michael B Elowitz

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

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  9. Article
  10. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  11. Article
  12. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Rongrong DuDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Michael J FlynnDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Karan MaheDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Monique HonsaFaculty of Physics, Center for Nanoscience, Ludwig Maximilian University, 80539 Munich, Germany; Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Bo GuDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Dongyang LiDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Sean E McGearyDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Viviana GradinaruDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Ralf JungmannFaculty of Physics, Center for Nanoscience, Ludwig Maximilian University, 80539 Munich, Germany; Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Michael B ElowitzDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: melowitz@caltech.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accurate control of transgene expression is important for research and therapy but is challenging to achieve in most settings. MicroRNA (miRNA)-based regulatory circuits can be incorporated within transgenes for improved control. However, the design principles, performance limits, and applications of these circuits in research and biotechnology have not been systematically determined. Here, combining modeling and experiments, we introduce miRNA-based circuit modules, termed "dosage invariant miRNA-mediated expression regulators" (DIMMERs), that establish precise, tunable control of transgene expression across diverse cell types to facilitate imaging, editing, and gene therapy. The circuits use multivalent miRNA regulatory interactions to achieve nearly uniform, tunable protein expression over two orders of magnitude variation in gene dosage. They function across diverse cell types and can be multiplexed for the independent regulation of multiple genes. DIMMERs reduce off-target CRISPR base editing, improve single-molecule imaging, and allow live tracking of adeno-associated virus (AAV)-delivered transgene expression in mouse cortical neurons. DIMMERs thus enable accurate regulation for research and biotechnology applications.

Indexed as

Gene Expression RegulationMicroRNAsAnimalsCRISPR-Cas SystemsDependovirusGene DosageGene EditingHEK293 CellsHumansMiceNeuronsTransgenesMicroRNAsdosage compensationgene therapymicroRNAmultispecific regulationprecise gene expression controlsynthetic biology

Identifiers

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.