Evidence map›Paper›PMID 41383011›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Targeted BDNF upregulation via upstream open reading frame disruption.

Ning Feng, Thomas Goedert, Nenad Svrzikapa, Dongnan Yan, Hans J Friedrichsen, Britt Hanson, Alicia Ljungdahl, Ruxandra Dafinca, Kevin Talbot, Stephan J Sanders and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Functional analysis ofMolecular therapy. Nucleic acids · 2026
    Article
  2. An upstream open reading frame represses translation of the neuronal potassium channel KCNQ2.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
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

13 authors.

Ning FengInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK.
Thomas GoedertInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK.
Nenad SvrzikapaDepartment of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Orfonyx Bio Ltd, BioEscalator, University of Oxford, Innovation Building, Rm 10.15, Roosevelt Drive, Oxford OX3 7FZ, UK.
Dongnan YanInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Hans J FriedrichsenInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK.
Britt HansonDepartment of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Alicia LjungdahlInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK.
Ruxandra DafincaOxford Motor Neuron Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Kevin TalbotOxford Motor Neuron Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Stephan J SandersInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; New York Genome Center, New York, NY 10013, USA.
Dhanu GuptaInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK.
Mathew J A WoodInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; MDUK Oxford Neuromuscular Centre, Oxford OX3 7TY, UK.
Thomas C RobertsInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Paediatrics, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; MDUK Oxford Neuromuscular Centre, Oxford OX3 7TY, UK. Electronic address: thomas.roberts@idrm.ox.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To understand the relative contributions of 5' UTR elements to translation output, we performed a comprehensive analysis of upstream open reading frames (uORFs) in the 5' UTRs of the BDNF (brain-derived neurotrophic factor) transcripts. Predicted uORFs were identified in 14 out of 17 BDNF RefSeq transcript isoforms, and we experimentally validated five of these transcripts as being uORF-repressed, suggesting that uORF elements play an important role in shaping the protein output from this locus. We explored several approaches to disrupt BDNF uORF function. Deletion of a 5' UTR exon in BDNF v11 (containing eight predicted uORFs), in order to simulate an exon skipping outcome, resulted in pronounced upregulation in a reporter construct system. This effect was found to be partially uORF-dependent but was also dependent on the disruption of an RNA secondary structure element. However, this transcript variant was found to not be expressed in human brain. Conversely, direct disruption of a single uORF start codon in the widely expressed BDNF v4 transcript variant using an adenine base editing approach resulted in a ∼1.8-fold upregulation of endogenous BDNF protein expression in cell culture. This study characterizes uORF-mediated regulation of the BDNF locus and demonstrates the potential for BDNF protein upregulation via base editing-mediated uORF disruption.

Indexed as

Brain-Derived Neurotrophic FactorOpen Reading FramesUp-Regulation5' Untranslated RegionsCodon, InitiatorExonsGene Expression RegulationHumansRNA, Messenger5' Untranslated RegionsBrain-Derived Neurotrophic FactorCodon, InitiatorRNA, Messengerbase editingBDNFbrain-derived neurotrophic factoruORFupstream open reading frame

Identifiers

PMID41383011
PMCPMC12974206

What OpenQuestion holds

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LicenceCC BY
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.