Evidence map›Paper›PMID 41830765›Full record

ArticleBiomaterials2026

Extracellular vesicles-mediated delivery of SpCas9 RNPs for therapeutic gene editing in Spinocerebellar Ataxia Type 3.

Kevin Leandro, David Rufino-Ramos, Sara M Lopes, Francisca Santos Silva, Paulo Rodrigues-Santos, Ana Carolina Silva, Ana Rita Fernandes, Carina Henriques, Dina Pereira, Diana Lobo and 6 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Kevin LeandroCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
David Rufino-RamosCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA; Department of Pathology, Harvard Medical School, Boston, MA, USA.
Sara M LopesCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Francisca Santos SilvaCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Paulo Rodrigues-SantosCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute of Immunology, Faculty of Medicine, University of Coimbra, Portugal.
Ana Carolina SilvaCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Ana Rita FernandesCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Carina HenriquesCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Dina PereiraCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Diana LoboCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Guilherme L GabrielCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Rosário FaroCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Rui Jorge NobreCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal; ViraVector, University of Coimbra, Coimbra, Portugal.
Pedro R L PerdigãoCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal.
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA; Department of Pathology, Harvard Medical School, Boston, MA, USA.
Luís Pereira de AlmeidaCNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; GeneT - Gene Therapy Center of Excellence Portugal, University of Coimbra, Coimbra, Portugal; ViraVector, University of Coimbra, Coimbra, Portugal. Electronic address: luispa@cnc.uc.pt.

Funding

PROJECT 4: Somatic evolution of the hematopoietic system in cardiovascular diseaseP01HL142494 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Matthias Nahrendorf · 2019 to 2026
$19.5M
NHLBI NIH HHS P01 HL142494
6 · The paper itself

Abstract

Spinocerebellar Ataxia Type 3 (SCA3) is a neurodegenerative dominantly-inherited disorder caused by an overexpansion of a CAG tract within the ATXN3 gene, conferring toxic properties to the ataxin-3 protein. Genome editing with CRISPR-Cas9 enzymes is a promising strategy to inactivate mutant ATXN3 alleles, however, in vivo delivery remains challenging. Extracellular vesicles (EVs) are promising delivery vehicles for Cas9 and single guide RNA (sgRNA) ribonucleoproteins that minimize genomic exposure to highly active endonucleases. In this study, we designed SpCas9 with a palmitoylation motif that enables SpCas9 and sgRNA enrichment into EVs. Introduction of a photocleavable linker - PhoCl - allowed the photo-inducible release of SpCas9 from the palmitoylation motif in EVs, increasing target engagement to ATXN3 in vitro. EVs loaded with SpCas9 ribonucleoproteins resulted in ATXN3 knockout in SCA3 patient-derived iPSCs and two SCA3 animal models. These findings highlight an innovative route for transient delivery of gene editing tools. This approach provides a promising therapeutic platform for the treatment of genetic diseases, including SCA3.

Indexed as

Ataxin-3Extracellular VesiclesInduced Pluripotent Stem CellsRNA, Guide, CRISPR-Cas SystemsAnimalsCRISPR-Associated Protein 9Gene EditingHumansMiceRepressor ProteinsAtaxin-3CRISPR-Associated Protein 9Repressor ProteinsRNA, Guide, CRISPR-Cas SystemsCRISPR-Cas9Extracellular vesiclesGene editingMachado-Joseph diseaseSpinocerebellar ataxia type 3

Identifiers

PMID41830765
PMCPMC13288182

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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.