Evidence map›Paper›PMID 41686893›Full record

ArticleScience advances2026

Accessory microRNA byproducts expand RNA interference via microprocessor-mediated cleavage activation.

Debora Mazzetti, Michal O Nowicki, Himanshu Soni, Joshua D Bernstock, Maya Groff, Luisa Esposito, Diego A Hernandez, Lucia Altucci, Anna Krichevsky, Geoffrey Fell and 4 more

Abstract read
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Debora MazzettiHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.ORCID 0009-0008-1767-7815
Michal O NowickiHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.ORCID 0000-0002-5807-0007
Himanshu SoniHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.
Joshua D BernstockHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.ORCID 0000-0002-7814-3867
Maya GroffGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Luisa EspositoDepartment of Oncology, Università La Sapienza of Rome, Italy.
Diego A HernandezHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.ORCID 0009-0005-7321-1604
Lucia AltucciDepartment of Precision Medicine, Università della Campania Luigi Vanvitelli, Naples, Italy.ORCID 0000-0002-7312-5387
Anna KrichevskyHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-5080-5507
Geoffrey FellDepartment of Data Science, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA.ORCID 0000-0001-6436-6691
E Antonio ChioccaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.
Hiroshi NakashimaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.ORCID 0000-0001-5425-9999
Marco MineoHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.ORCID 0000-0001-7608-4579
Pierpaolo PeruzziHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Mass General Brigham, Boston, MA, USA.ORCID 0000-0001-5034-2963

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA medicine is a promisingly expanding field in modern health care, but its use in genetically complex diseases, like cancer, has been challenging, mainly due to their reliance on multiple abnormal pathways. Here, we describe a microRNA-based platform that exploits previously unrecognized features of microRNA processing. Leveraging a microprocessor-dependent, cleave-activation strategy, this design allows us to expand biological impact by simultaneously up- and down-regulating desired microRNAs, while using them as structural enablers for other short, noncoding RNAs, such as aptamers. We demonstrate its biological potential in a glioblastoma model, where the simultaneous bidirectional modulation of five among the most deregulated microRNAs results in critical mass interference against the tumor. In parallel, microRNA-mediated chaperoning of an anti-p50 aptamer within the platform allows us to selectively block the nuclear factor κB pathway, a difficult-to-drug target. This work highlights the potential of chimeric microRNA clusters as an emerging therapeutic concept for cancer and other similarly multifactorial diseases.

Indexed as

MicroRNAsRNA InterferenceAptamers, NucleotideCell Line, TumorGene Expression Regulation, NeoplasticGlioblastomaHumansNF-kappa BAptamers, NucleotideMicroRNAsNF-kappa B

Identifiers

PMID41686893
PMCPMC12904199

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Registered trials

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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.