Evidence map›Paper›PMID 40759644›Full record

ArticleNature communications2025

Computational identification of small molecules for increased gene expression by synthetic circuits in mammalian cells.

M Pisani, F Calandra, A Rinaldi, F Cella, F Tedeschi, I Boffa, D Vozzi, N Brunetti-Pierri, A Carissimo, F Napolitano and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Breeding ofBiodesign research · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Review
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

11 authors.

M PisaniSynthetic and Systems Biology lab for Biomedicine, Istituto Italiano di Tecnologia-IIT, Naples, Italy.ORCID http://orcid.org/0009-0004-2193-1805
F CalandraSynthetic and Systems Biology lab for Biomedicine, Istituto Italiano di Tecnologia-IIT, Naples, Italy.ORCID http://orcid.org/0009-0002-1308-9967
A RinaldiSynthetic and Systems Biology lab for Biomedicine, Istituto Italiano di Tecnologia-IIT, Naples, Italy.ORCID http://orcid.org/0000-0001-8854-6048
F CellaSynthetic and Systems Biology lab for Biomedicine, Istituto Italiano di Tecnologia-IIT, Naples, Italy.
F TedeschiSynthetic and Systems Biology lab for Biomedicine, Istituto Italiano di Tecnologia-IIT, Naples, Italy.
I BoffaTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
D VozziIstituto Italiano di Tecnologia-IIT, Genoa, Italy.
N Brunetti-PierriTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.ORCID http://orcid.org/0000-0002-6895-8819
A CarissimoIstituto per le Applicazioni del Calcolo "Mauro Picone", Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
F NapolitanoDepartment of Science and Technology, University of Sannio, Benevento, Italy.ORCID http://orcid.org/0000-0002-7782-8506
V SicilianoSynthetic and Systems Biology lab for Biomedicine, Istituto Italiano di Tecnologia-IIT, Naples, Italy. velia.siciliano@iit.it.ORCID http://orcid.org/0000-0001-7734-9153

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Engineering mammalian cells with synthetic circuits drives innovation in next-generation biotherapeutics and industrial biotechnology. However, applications often depend on cellular productivity, which is constrained by finite cellular resources. Here, we harness computational biology to identify drugs that boost productivity without additional genetic modifications. We perform RNA-sequencing on cells expressing an incoherent feed-forward loop (iFFL), a genetic circuit that enhances operational capacity. To find drugs that mimic this effect, we use DECCODE (Drug Enhanced Cell COnversion using Differential Expression), an unbiased method that matches our transcriptional data with thousands of drug-induced profiles. Among the compound candidates, we select Filgotinib, that enhances expression of both transiently and stably expressed genetic payloads across various experimental scenarios and cell lines, including AAV and lentivirus transduction. Our results reveal cell-specific responses, underscoring the context dependency of small-molecule treatments. Altogether, we present a versatile tool for biomedical and industrial applications requiring enhanced productivity from engineered cells.

Indexed as

Computational BiologyGene ExpressionGene Expression RegulationGene Regulatory NetworksSmall Molecule LibrariesAnimalsHEK293 CellsHumansSynthetic BiologySmall Molecule Libraries

Identifiers

PMID40759644
PMCPMC12322086

What OpenQuestion holds

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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.