Evidence map›Paper›PMID 34795295›Full record

ArticleNature communications2021

GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain.

Ghulam Hassan Dar, Cláudia C Mendes, Wei-Li Kuan, Alfina A Speciale, Mariana Conceição, André Görgens, Inna Uliyakina, Miguel J Lobo, Wooi F Lim, Samir El Andaloussi and 6 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
5.1field-weighted citation impact, top 3% of its field
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

66 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
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  5. Subcellular localization as a driver of protein function.Nature reviews. Molecular cell biology · 2026
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  14. First In Silico Study of TwoInternational journal of molecular sciences · 2025
    Article
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  17. Review
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  20. Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Ghulam Hassan DarDepartment of Paediatrics, University of Oxford, Oxford, OX1 3QX, UK.
Cláudia C MendesDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
Wei-Li KuanJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0PY, UK.
Alfina A SpecialeDepartment of Paediatrics, University of Oxford, Oxford, OX1 3QX, UK.ORCID http://orcid.org/0000-0001-9728-254X
Mariana ConceiçãoDepartment of Paediatrics, University of Oxford, Oxford, OX1 3QX, UK.
André GörgensDepartment of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, 14186, Stockholme, Sweden.ORCID http://orcid.org/0000-0001-9198-0857
Inna UliyakinaDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
Miguel J LoboDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
Wooi F LimDepartment of Paediatrics, University of Oxford, Oxford, OX1 3QX, UK.ORCID http://orcid.org/0000-0002-1238-3040
Samir El AndaloussiDepartment of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, 14186, Stockholme, Sweden.ORCID http://orcid.org/0000-0003-4468-9113
Imre MägerDepartment of Paediatrics, University of Oxford, Oxford, OX1 3QX, UK.ORCID http://orcid.org/0000-0003-2242-7227
Thomas C RobertsDepartment of Paediatrics, University of Oxford, Oxford, OX1 3QX, UK.ORCID http://orcid.org/0000-0002-3313-7631
Roger A BarkerJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0PY, UK.
Deborah C I GoberdhanDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.ORCID http://orcid.org/0000-0003-0645-6714
Clive WilsonDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK. clive.wilson@dpag.ox.ac.uk.
Matthew J A WoodDepartment of Paediatrics, University of Oxford, Oxford, OX1 3QX, UK. matthew.wood@paediatrics.ox.ac.uk.ORCID http://orcid.org/0000-0002-5436-6011
University of Oxford · GBKarolinska Institutet · SEUniversity of Cambridge · GB

Funding

Biotechnology and Biological Sciences Research Council BB/K017462/1Biotechnology and Biological Sciences Research Council BB/N016300/1Biotechnology and Biological Sciences Research Council BB/R004862/1Cancer Research UK 19076Cancer Research UK C19591/A19076Medical Research Council MC_PC_17174Medical Research Council MR/M007715/1Wellcome TrustWellcome Trust 102347/Z/13/Z
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication, and potential as drug delivery vehicles. Here we demonstrate a role for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in EV assembly and secretion. We observe high levels of GAPDH binding to the outer surface of EVs via a phosphatidylserine binding motif (G58), which promotes extensive EV clustering. Further studies in a Drosophila EV biogenesis model reveal that GAPDH is required for the normal generation of intraluminal vesicles in endosomal compartments, and promotes vesicle clustering. Fusion of the GAPDH-derived G58 peptide to dsRNA-binding motifs enables highly efficient loading of small interfering RNA (siRNA) onto the EV surface. Such vesicles efficiently deliver siRNA to multiple anatomical regions of the brain in a Huntington's disease mouse model after systemic injection, resulting in silencing of the huntingtin gene in different regions of the brain.

Indexed as

AnimalsBrainCell Line, TumorDisease Models, AnimalDrug Delivery SystemsExtracellular VesiclesGlyceraldehyde-3-Phosphate DehydrogenasesHEK293 CellsHeLa CellsHumansHuntingtin ProteinHuntington DiseaseMesenchymal Stem CellsMiceMice, Inbred C57BLPhosphatidylserinesGlyceraldehyde-3-Phosphate DehydrogenasesHuntingtin ProteinPhosphatidylserinesRNA, Small Interfering

Identifiers

PMID34795295
PMCPMC8602309
OpenAlexW3214573095

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.