{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:31:15Z","timestamp":1793377875379,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001348","name":"A*STAR Research Entities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.ymthe.2026.08.018","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:48:20Z","timestamp":1786463300000},"page":"5970-5992","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unlocking extracellular vesicle-mediated efficient DNA delivery for long-lasting transgene expression"],"prefix":"10.1016","volume":"34","author":[{"given":"Melissa","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Kawamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odom","family":"Seng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Eagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evonne","family":"Ip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desmond Wai Loon","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Zhong","family":"Leong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Goh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harwin","family":"Sidik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1938-6954","authenticated-orcid":false,"given":"Trinh T.T.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozan","family":"Alkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronne","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Haut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenzin","family":"Gocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6077-1566","authenticated-orcid":false,"given":"Minh T.N.","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waqas Muhammad","family":"Usman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2026.08.018_bib1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-021-00487-6","article-title":"Viral vector platforms within the gene therapy landscape","volume":"6","author":"Bulcha","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.ymthe.2026.08.018_bib2","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41565-021-00898-0","article-title":"The current landscape of nucleic acid therapeutics","volume":"16","author":"Kulkarni","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib3","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s12951-023-02044-5","article-title":"Emerging non-viral vectors for gene delivery","volume":"21","author":"Wang","year":"2023","journal-title":"J. Nanobiotechnology"},{"key":"10.1016\/j.ymthe.2026.08.018_bib4","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nm1358","article-title":"Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response","volume":"12","author":"Manno","year":"2006","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2026.08.018_bib5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno-associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.ymthe.2026.08.018_bib6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.omtm.2021.08.002","article-title":"Quantitative analysis of genome packaging in recombinant AAV vectors by charge detection mass spectrometry","volume":"23","author":"Barnes","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2026.08.018_bib7","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"10.1016\/j.ymthe.2026.08.018_bib8","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1038\/s12276-023-01086-x","article-title":"Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics","volume":"55","author":"Lee","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.ymthe.2026.08.018_bib9","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41551-024-01227-1","article-title":"Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing","volume":"9","author":"Pandey","year":"2025","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.ymthe.2026.08.018_bib10","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1038\/s41598-017-02456-y","article-title":"An episomal vector-based CRISPR\/Cas9 system for highly efficient gene knockout in human pluripotent stem cells","volume":"7","author":"Xie","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2026.08.018_bib11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrd3978","article-title":"Extracellular vesicles: biology and emerging therapeutic opportunities","volume":"12","author":"El Andaloussi","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ymthe.2026.08.018_bib12","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/s12276-024-01201-6","article-title":"Recent advances in extracellular vesicles for therapeutic cargo delivery","volume":"56","author":"Kim","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.ymthe.2026.08.018_bib13","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.semcancer.2020.08.007","article-title":"Extracellular vesicles as natural therapeutic agents and innate drug delivery systems for cancer treatment: Recent advances, current obstacles, and challenges for clinical translation","volume":"80","author":"Pirisinu","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib14","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41565-021-00931-2","article-title":"Extracellular vesicles as a next-generation drug delivery platform","volume":"16","author":"Herrmann","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib15","doi-asserted-by":"crossref","first-page":"738","DOI":"10.3389\/fimmu.2018.00738","article-title":"Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression","volume":"30","author":"Willms","year":"2018","journal-title":"Front Immunol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib16","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.semcancer.2021.02.010","article-title":"New approaches in extracellular vesicle engineering for improving the efficacy of anti-cancer therapies","volume":"74","author":"Jayasinghe","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib17","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.jcyt.2018.12.006","article-title":"Manufacturing and characterization of extracellular vesicles from umbilical cord\u2013derived mesenchymal stromal cells for clinical testing","volume":"21","author":"Rohde","year":"2019","journal-title":"Cytotherapy"},{"key":"10.1016\/j.ymthe.2026.08.018_bib18","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12266","article-title":"Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles","author":"Visan","year":"2022","journal-title":"J. Extracell Vesicles."},{"key":"10.1016\/j.ymthe.2026.08.018_bib19","doi-asserted-by":"crossref","first-page":"10131","DOI":"10.1073\/pnas.1409861111","article-title":"Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes","volume":"111","author":"Shi","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2026.08.018_bib20","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1038\/s41467-018-04791-8","article-title":"Efficient RNA drug delivery using red blood cell extracellular vesicles","volume":"9","author":"Usman","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2026.08.018_bib21","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.7150\/thno.68667","article-title":"Surface-engineered extracellular vesicles for targeted delivery of therapeutic RNAs and peptides for cancer therapy","volume":"12","author":"Jayasinghe","year":"2022","journal-title":"Theranostics"},{"key":"10.1016\/j.ymthe.2026.08.018_bib22","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12187","article-title":"Robust delivery of RIG-I agonists using extracellular vesicles for anti-cancer immunotherapy","volume":"11","author":"Peng","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.ymthe.2026.08.018_bib23","doi-asserted-by":"crossref","first-page":"21639","DOI":"10.1021\/acsnano.3c06803","article-title":"Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy","volume":"17","author":"Jayasinghe","year":"2023","journal-title":"ACS Nano"},{"key":"10.1016\/j.ymthe.2026.08.018_bib24","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1016\/j.ymthe.2023.03.036","article-title":"Red blood cell extracellular vesicles deliver therapeutic siRNAs to skeletal muscles for treatment of cancer cachexia","volume":"31","author":"Peng","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2026.08.018_bib25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1021\/acsomega.2c06768","article-title":"Oxidants and Antioxidants in the Redox Biochemistry of Human Red Blood Cells","volume":"8","author":"M\u00f6ller","year":"2023","journal-title":"ACS Omega"},{"key":"10.1016\/j.ymthe.2026.08.018_bib26","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3389\/fphys.2015.00096","article-title":"Extracellular hemoglobin: the case of a friend turned foe","volume":"6","author":"Quaye","year":"2015","journal-title":"Front. Physiol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib27","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/s41577-018-0005-7","article-title":"Nonhuman primate models of human viral infections","volume":"18","author":"Estes","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/23144599.2019.1704992","article-title":"Preservation techniques of stem cells extracellular vesicles: a gate for manufacturing of clinical grade therapeutic extracellular vesicles and long-term clinical trials","volume":"8","author":"Bahr","year":"2020","journal-title":"Int. J. Vet. Sci. Med."},{"key":"10.1016\/j.ymthe.2026.08.018_bib29","doi-asserted-by":"crossref","DOI":"10.1038\/srep36162","article-title":"Trehalose prevents aggregation of exosomes and cryodamage","volume":"6","author":"Bosch","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2026.08.018_bib30","doi-asserted-by":"crossref","first-page":"e241","DOI":"10.1016\/S2352-3026(18)30053-X","article-title":"Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study","volume":"5","author":"Lane","year":"2018","journal-title":"Lancet Haematol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib31","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1182\/blood-2018-11-833954","article-title":"Blood group genotyping","volume":"133","author":"Westhoff","year":"2019","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2026.08.018_bib32","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1021\/acs.molpharmaceut.7b00950","article-title":"Role of Extracellular Vesicle Surface Proteins in the Pharmacokinetics of Extracellular Vesicles","volume":"15","author":"Charoenviriyakul","year":"2018","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.ymthe.2026.08.018_bib33","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/gt.2016.23","article-title":"Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice","volume":"23","author":"Anderson","year":"2016","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2026.08.018_bib34","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1177\/2040620718796429","article-title":"Practical aspects of extended half-life products for the treatment of haemophilia","volume":"9","author":"Lambert","year":"2018","journal-title":"Ther. Adv. Hematol."},{"key":"10.1016\/j.ymthe.2026.08.018_bib35","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/cgt.2016.37","article-title":"Gene therapy using plasmid DNA-encoded anti-HER2 antibody for cancers that overexpress HER2","volume":"23","author":"Kim","year":"2016","journal-title":"Cancer Gene Ther."},{"key":"10.1016\/j.ymthe.2026.08.018_bib36","doi-asserted-by":"crossref","first-page":"5886","DOI":"10.1038\/s41467-022-33309-6","article-title":"DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2","volume":"13","author":"Parzych","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2026.08.018_bib37","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1038\/s12276-023-01118-6","article-title":"Understanding nucleic acid sensing and its therapeutic applications","volume":"55","author":"Kong","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.ymthe.2026.08.018_bib38","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2026.08.018_bib39","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12085","article-title":"Biodistribution of extracellular vesicles following administration into animals: A systematic review","volume":"10","author":"Kang","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.ymthe.2026.08.018_bib40","doi-asserted-by":"crossref","DOI":"10.3402\/jev.v4.26316","article-title":"Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting","volume":"4","author":"Wiklander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.ymthe.2026.08.018_bib41","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1186\/1471-2164-9-488","article-title":"BioVenn \u2013 a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams","volume":"9","author":"Hulsen","year":"2008","journal-title":"BMC Genomics"},{"key":"10.1016\/j.ymthe.2026.08.018_bib42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2026.08.018_bib43","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"10.1016\/j.ymthe.2026.08.018_bib44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/pro.4218","article-title":"PANTHER: Making genome-scale phylogenetics accessible to all","volume":"31","author":"Thomas","year":"2022","journal-title":"Protein Sci."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001626007008?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001626007008?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:34:18Z","timestamp":1793374458000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001626007008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["S1525001626007008"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2026.08.018","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Unlocking extracellular vesicle-mediated efficient DNA delivery for long-lasting transgene expression","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2026.08.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}