Evidence map›Paper›PMID 41271724›Full record

ArticleNature communications2025

A modular strategy for extracellular vesicle-mediated CRISPR-Cas9 delivery through aptamer-based loading and UV-activated cargo release.

Omnia M Elsharkasy, Charlotte V Hegeman, Tom A P Driedonks, Xiuming Liang, Ivana Lansweers, Olaf L Cotugno, Ingmar Y de Groot, Zoë E M N J de Wit, Antonio Garcia-Guerra, Niels J A Moorman and 12 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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

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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

22 authors.

Omnia M Elsharkasy *CDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Charlotte V Hegeman *Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-7095-8834
Tom A P DriedonksCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0003-0928-9712
Xiuming LiangDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0202-1211
Ivana LansweersDepartment of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Olaf L CotugnoCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Ingmar Y de GrootCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Zoë E M N J de WitDepartment of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Antonio Garcia-GuerraDepartment of Paediatrics, University of Oxford, Oxford, United Kingdom.
Niels J A MoormanDepartment of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Sjoerd H BoonstraDepartment of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Esmeralda D C BosmanDepartment of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Juliet W LeffertsDepartment of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Willemijn S de VoogtCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0009-0008-7876-5018
Jerney J FrançoisCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Annet C W van WeselCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Samir El AndaloussiDivision for Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-4468-9113
Raymond M SchiffelersCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0009-0004-2423-209X
Sander A A KooijmansCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-8893-9578
Enrico MastrobattistaDepartment of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-6745-2015
Pieter VaderCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-7059-8920
Olivier G de JongCDL Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. o.g.dejong@uu.nl.ORCID http://orcid.org/0000-0002-5952-9617

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) VI.Veni.192.174
6 · The paper itself

Abstract

CRISPR-Cas9 gene editing technology offers the potential to permanently repair genes containing pathological mutations. However, efficient intracellular delivery of the Cas9 ribonucleoprotein complex remains a major hurdle in its therapeutic application. Extracellular vesicles (EVs) are biological nanosized membrane vesicles that play an important role in intercellular communication, and have an innate capability of intercellular transfer of biological cargos, including proteins and RNA. Here, we present a versatile, modular strategy for EV-mediated loading and delivery of Cas9. We leverage the high affinity binding of MS2 coat proteins fused to EV-enriched proteins to MS2 aptamers incorporated into guide RNAs, in combination with a UV-activated photocleavable linker domain, PhoCl. Moreover, we demonstrate that Cas9 can readily be exchanged for other variants, including transcriptional activator dCas9-VPR and adenine base editor ABE8e. Taken together, we describe a robust, modular strategy for successful Cas9 delivery, which can be applied for CRISPR-Cas9-based genetic engineering and transcriptional regulation.

Indexed as

Aptamers, NucleotideCRISPR-Cas SystemsExtracellular VesiclesGene EditingCRISPR-Associated Protein 9HEK293 CellsHumansRNA, Guide, CRISPR-Cas SystemsUltraviolet RaysAptamers, NucleotideCRISPR-Associated Protein 9RNA, Guide, CRISPR-Cas Systems

Identifiers

PMID41271724
PMCPMC12639036

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.