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Exosome-like nanovesicles from acerola for CRISPR-Cas9 ribonucleoprotein delivery to the central nervous system.

Overview

Authors: Yui Nagamatsu1, Tomohiro Umezu1, Taehun Hong1, Takahide Niijima1, Shin-ichiro Ohno1, Yuichiro Harada1, Kohsuke Kanekura2, Takahiro Ochiya3, Masahiko Kuroda1
  1. Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan
  2. Department of Pharmacology, Tokyo Medical University, Tokyo, Japan
  3. Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan
Institutions: Tokyo Medical University (Japan)
Journal: Molecular therapy. Nucleic acids, volume 37, issue 2, article 102896
Dates: received 23 September 2025; accepted 9 March 2026; published online 12 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.omtn.2026.102896 · PMID 41909467 · PMCID PMC13022685 · OpenAlex W7135031237
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: other condition (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, Connectivity, fMRI & imaging
Keywords: MT: Delivery Strategies, acerola, blood-brain barrier, central nervous system, CRISPR/Cas9, drug delivery, neurodegenerative disease, plant-derived exosomes
Topic: Extracellular vesicles in disease (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Japan Agency for Medical Research and Development (JP25ym0126183h0001)
Citations: cited by 1 paper (Europe PMC); 34 references in the paper

Abstract

An aberrant six-base repeat in intron 1 of C9orf72 is the most frequent cause of solitary and familial amyotrophic lateral sclerosis and frontotemporal dementia. This mutation is a potential target for CRISPR/Cas9-based genome editing. However, the blood-brain barrier and limitations of current viral or nanoparticle-based delivery systems to neurons significantly restrict the clinical application of CRISPR-Cas9 in the brain. To address these challenges, we developed a drug delivery system using acerola-derived exosome-like nanoparticles (AELNs), which may overcome several limitations associated with human exosomes. AELNs stably form complexes with ribonucleoproteins (RNPs) comprised of Cas9 proteins and guide RNAs (gRNAs). We improved the delivery efficiency and selectivity of AELN/RNP complexes in GLP2-receptor-expressing neurons by incorporating GLP2 peptides into the AELN/RNP complexes. Intranasal administration of peptide-tagged AELN/RNP complexes in vivo confirmed the successful genome editing of C9orf72, demonstrating the potential of this system for treating neurodegenerative diseases. This study presents a potentially innovative approach for in vivo genome editing using a noninvasive delivery system.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

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Data and code availability

The datasets generated and/or analyzed during the current study are not publicly available due to ongoing patent applications and intellectual property considerations; however, they are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 8 keywords, 1 funder, 34 references.

Cite

This paper

Nagamatsu, Y., Umezu, T., Hong, T., Niijima, T., Ohno, S.-i., Harada, Y., Kanekura, K., Ochiya, T., & Kuroda, M. (2026). Exosome-like nanovesicles from acerola for CRISPR-Cas9 ribonucleoprotein delivery to the central nervous system. Molecular therapy. Nucleic acids, 37(2), 102896. https://doi.org/10.1016/j.omtn.2026.102896

BibTeX

@article{nagamatsu2026exosome,
author = {Nagamatsu, Yui and Umezu, Tomohiro and Hong, Taehun and Niijima, Takahide and Ohno, Shin-ichiro and Harada, Yuichiro and Kanekura, Kohsuke and Ochiya, Takahiro and Kuroda, Masahiko},
title = {{Exosome-like nanovesicles from acerola for CRISPR-Cas9 ribonucleoprotein delivery to the central nervous system}},
journal = {Molecular therapy. Nucleic acids},
year = {2026},
month = mar,
volume = {37},
number = {2},
pages = {102896},
publisher = {American Society of Gene \& Cell Therapy},
issn = {2162-2531},
doi = {10.1016/j.omtn.2026.102896},
url = {https://doi.org/10.1016/j.omtn.2026.102896},
pmid = {41909467},
pmcid = {PMC13022685}
}

RIS

TY - JOUR
AU - Nagamatsu, Yui
AU - Umezu, Tomohiro
AU - Hong, Taehun
AU - Niijima, Takahide
AU - Ohno, Shin-ichiro
AU - Harada, Yuichiro
AU - Kanekura, Kohsuke
AU - Ochiya, Takahiro
AU - Kuroda, Masahiko
TI - Exosome-like nanovesicles from acerola for CRISPR-Cas9 ribonucleoprotein delivery to the central nervous system
T2 - Molecular therapy. Nucleic acids
J2 - Mol Ther Nucleic Acids
PY - 2026
DA - 2026/03/12
VL - 37
IS - 2
SP - 102896
SN - 2162-2531
PB - American Society of Gene & Cell Therapy
DO - 10.1016/j.omtn.2026.102896
UR - https://doi.org/10.1016/j.omtn.2026.102896
LA - en
ER -

CSL-JSON

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