Evidence map›Paper›PMID 40301355›Full record

ArticleNature communications2025

Engineering of extracellular vesicles for efficient intracellular delivery of multimodal therapeutics including genome editors.

Xiuming Liang, Dhanu Gupta, Junhua Xie, Elien Van Wonterghem, Lien Van Hoecke, Justin Hean, Zheyu Niu, Marziyeh Ghaeidamini, Oscar P B Wiklander, Wenyi Zheng and 28 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 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing 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

63 citing papers in PubMed.

  1. Overview of Delivery Methods for Gene Editing.Methods in molecular biology (Clifton, N.J.) · 2027
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  15. Endogenous Engineering Reprograms Extracellular Vesicles for Enhanced Therapeutic Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  17. Navigating theNanoscale advances · 2026
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3 more citing papers are in PubMed but not listed here.

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

38 authors.

Xiuming LiangDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. xiuming.liang@ki.se.ORCID http://orcid.org/0000-0003-0202-1211
Dhanu Gupta *Division for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0163-2678
Junhua Xie *VIB Center for Inflammation Research, VIB, 9052, Ghent, Belgium.
Elien Van WonterghemVIB Center for Inflammation Research, VIB, 9052, Ghent, Belgium.
Lien Van HoeckeVIB Center for Inflammation Research, VIB, 9052, Ghent, Belgium.
Justin HeanEvox Therapeutics Limited, Oxford, United Kingdom.
Zheyu NiuDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Marziyeh GhaeidaminiDivision of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, 41296, Göteborg, Sweden.
Oscar P B WiklanderDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-1176-8114
Wenyi ZhengDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2416-5822
Rim Jawad WiklanderDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Rui HeExperimental Cancer Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet., Stockholm, Sweden.
Doste R MamandDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Jeremy BostDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-3804-0521
Guannan ZhouDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Houze ZhouDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Samantha RoudiDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-3923-3410
H Yesid EstupiñánDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-9388-5957
Julia RädlerDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-4839-3822
Antje M ZicklerDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-5001-6586
André GörgensDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-9198-0857
Vicky W Q HouDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Radka SlovakEvox Therapeutics Limited, Oxford, United Kingdom.ORCID http://orcid.org/0000-0002-9963-5975
Daniel W HageyDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-9246-6235
Olivier G de JongDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, 3584 CG, The Netherlands.ORCID http://orcid.org/0000-0002-5952-9617
Aileen Geobee UyDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Yuanyuan ZongDepartment of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250021, PR China.
Imre MägerInstitute of Technology, University of Tartu, 50 411, Tartu, Estonia.ORCID http://orcid.org/0000-0003-2242-7227
Carla Martin PerezInstitute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, 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.ORCID http://orcid.org/0000-0002-3313-7631
Dave CarterEvox Therapeutics Limited, Oxford, United Kingdom.
Pieter VaderCDL Research, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0002-7059-8920
Elin K EsbjörnerDivision of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, 41296, Göteborg, Sweden.ORCID http://orcid.org/0000-0002-1253-6342
Antonin de FougerollesEvox Therapeutics Limited, Oxford, United Kingdom.
Matthew 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.
Roosmarijn E VandenbrouckeVIB Center for Inflammation Research, VIB, 9052, Ghent, Belgium.ORCID http://orcid.org/0000-0002-8327-620X
Joel Z NordinDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. joel.nordin@ki.se.ORCID http://orcid.org/0000-0002-3653-7710
Samir El AndaloussiDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. samir.el-andaloussi@ki.se.ORCID http://orcid.org/0000-0003-4468-9113

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracellular delivery of protein and RNA therapeutics represents a major challenge. Here, we develop highly potent engineered extracellular vesicles (EVs) by incorporating bio-inspired attributes required for effective delivery. These comprise an engineered mini-intein protein with self-cleavage activity for active cargo loading and release, and fusogenic VSV-G protein for endosomal escape. Combining these components allows high efficiency recombination and genome editing in vitro following EV-mediated delivery of Cre recombinase and Cas9/sgRNA RNP cargoes, respectively. In vivo, infusion of a single dose Cre loaded EVs into the lateral ventricle in brain of Cre-LoxP R26-LSL-tdTomato reporter mice results in greater than 40% and 30% recombined cells in hippocampus and cortex respectively. In addition, we demonstrate therapeutic potential of this platform by showing inhibition of LPS-induced systemic inflammation via delivery of a super-repressor of NF-ĸB activity. Our data establish these engineered EVs as a platform for effective delivery of multimodal therapeutic cargoes, including for efficient genome editing.

Indexed as

Drug Delivery SystemsExtracellular VesiclesGene EditingAnimalsCRISPR-Associated Protein 9CRISPR-Cas SystemsHEK293 CellsHumansInflammationIntegrasesMiceNF-kappa BCre recombinaseCRISPR-Associated Protein 9IntegrasesNF-kappa B

Identifiers

PMID40301355
PMCPMC12041237

What Socratic holds

Textmetadata
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 Socratic graph.