Evidence map›Paper›PMID 40527733›Full record

ArticleJournal of extracellular vesicles2025

Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery.

Wataru Obuchi, Ayrton Zargani-Piccardi, Kevin Leandro, David Rufino-Ramos, Emilio Di Lanni, Dawn Madison Frederick, Katia Maalouf, Lisa Nieland, Tianhe Xiao, Pierre Repiton and 7 more

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
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  4. Endogenous Engineering Reprograms Extracellular Vesicles for Enhanced Therapeutic Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

17 authors.

Wataru ObuchiDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ayrton Zargani-PiccardiDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Kevin LeandroDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
David Rufino-RamosCenter for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Emilio Di LanniDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Dawn Madison FrederickDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Katia MaaloufDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Lisa NielandDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Tianhe XiaoDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Pierre RepitonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Christine A VaineThe Collaborative Center for X-Linked Dystonia-Parkinsonism, Massachusetts General Hospital, Boston, Massachusetts, USA.
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
D Cristopher BraggDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Hakho LeeCenter for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Miles A MillerCenter for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Xandra O BreakefieldDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Koen BreyneDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-0713-2407

Funding

The power of extracellular vesicles in glioblastomaR35CA232103 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS · 2018 to 2024
$6.9M
Dissection of in situ myeloid signaling using image-guided synthetic controlDP2CA259675 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MILLER, MILES A · 2020 to 2023
$2.7M
Scalable Development of Custom Genome Editing TechnologiesDP2CA281401 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KLEINSTIVER, BENJAMIN PETER · 2022 to 2025
$2.5M
Molecular profiling of global tissue dynamics at sub cellular resolutionR01GM138790 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI MILLER, MILES A · 2022 to 2025
$1.3M
Boosting IL-12-induced anti-glioblastoma activity via immunotherapeutic extracellular vesicles.K22CA282019 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Koen Breyne · 2024 to 2026
$482k
Daiichi Sankyo CompanyFriedreich's Ataxia Research Alliance AustraliaIonis PharmaceuticalsKayden-Lambert MGH Research Scholar AwardNational Science Foundation NIH DP2-CA259675National Science Foundation NIH DP2-CA281401National Science Foundation NIH K22-CA2802019-01National Science Foundation NIH R01-GM138790NCI NIH HHS DP2 CA259675NCI NIH HHS DP2 CA281401NCI NIH HHS K22 CA282019NCI NIH HHS NCI-CA232103NCI NIH HHS R35 CA232103NIGMS NIH HHS R01 GM138790
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are mediators of intercellular communication through the transfer of nucleic acids, lipids and proteins between cells. This property makes bioengineered EVs promising therapeutic vectors. However, it remains challenging to isolate EVs with a therapeutic payload due to the heterogeneous nature of cargo loading into EVs. In this study, enrichment of EVs with a desired cargo was possible through engineering of the hallmark CD63 transmembrane protein. E-NoMi refers to engineered CD63 with mCherry on the inside of the EV membrane and a tag (3xFLAG) exposed on the outside of the EV membrane. To facilitate EV loading during biogenesis, cargo proteins, such as EGFP, Cre recombinase and the CRISPR-Cas nuclease (SaCas9), were fused to a nanobody (Nb) protein with a high affinity for mCherry. FLAG-tag-based immunocapture from cell conditioned media allowed selection of cargo-loaded E-NoMi-EVs, and tobacco etch virus (TEV) protease cleavage sites were used to remove the 3xFLAG-tag from the surface of E-NoMi-EVs after capture. For functional payload delivery to recipient cells, the vesicular stomatitis virus G (VSV-G) fusogenic protein was incorporated into E-NoMi-EVs to form fusogenic EV-based vectors (EVVs) and proved to be 10-fold more effective at cargo delivery than EVs generated by size-exclusion chromatography. Functional delivery of cargo with E-NoMi-EVVs was validated in two mouse brain models in vivo.

Indexed as

BioengineeringExtracellular VesiclesTetraspanin 30AnimalsBrainGlioblastomaHeterograftsHumansMiceNeural Stem CellsPeptide Elongation Factor 1Promoter Regions, GeneticRed Fluorescent ProteinCD63 protein, humanmCherry fluorescent proteinPeptide Elongation Factor 1Red Fluorescent ProteinTetraspanin 30Cre recombinaseCRISPRenveloped delivery vehiclesextracellular vesiclesgene therapyvirus‐like particles

Identifiers

PMID40527733
PMCPMC12173531

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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.