{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:28:13Z","timestamp":1781303293547,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["F-1101"],"award-info":[{"award-number":["F-1101"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["15627"],"award-info":[{"award-number":["15627"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["CPII20\/00027"],"award-info":[{"award-number":["CPII20\/00027"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Michael J Fox Foundation","award":["F-1101"],"award-info":[{"award-number":["F-1101"]}]},{"name":"Michael J Fox Foundation","award":["15627"],"award-info":[{"award-number":["15627"]}]},{"name":"Michael J Fox Foundation","award":["CPII20\/00027"],"award-info":[{"award-number":["CPII20\/00027"]}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["F-1101"],"award-info":[{"award-number":["F-1101"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["15627"],"award-info":[{"award-number":["15627"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["CPII20\/00027"],"award-info":[{"award-number":["CPII20\/00027"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The development of effective disease-modifying therapies to halt Parkinson\u2019s disease (PD) progression is required. In a subtype of PD patients, alpha-synuclein pathology may start in the enteric nervous system (ENS) or autonomic peripheral nervous system. Consequently, strategies to decrease the expression of alpha-synuclein in the ENS will be an approach to prevent PD progression at pre-clinical stages in these patients. In the present study, we aimed to assess if anti-alpha-synuclein shRNA-minicircles (MC) delivered by RVG-extracellular vesicles (RVG-EV) could downregulate alpha-synuclein expression in the intestine and spinal cord. RVG-EV containing shRNA-MC were injected intravenously in a PD mouse model, and alpha-synuclein downregulation was evaluated by qPCR and Western blot in the cord and distal intestine. Our results confirmed the downregulation of alpha-synuclein in the intestine and spinal cord of mice treated with the therapy. We demonstrated that the treatment with anti-alpha-synuclein shRNA-MC RVG-EV after the development of pathology is effective to downregulate alpha-synuclein expression in the brain as well as in the intestine and spinal cord. Moreover, we confirmed that a multidose treatment is necessary to maintain downregulation for long-term treatments. Our results support the potential use of anti-alpha-synuclein shRNA-MC RVG-EV as a therapy to delay or halt PD pathology progression.<\/jats:p>","DOI":"10.3390\/pharmaceutics15041230","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T04:33:26Z","timestamp":1681360406000},"page":"1230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeted Extracellular Vesicle Gene Therapy for Modulating Alpha-Synuclein Expression in Gut and Spinal Cord"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4807-6779","authenticated-orcid":false,"given":"Maria","family":"Izco","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Piqueras 98, 3th Floor, 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schleef","sequence":"additional","affiliation":[{"name":"PlasmidFactory GmbH & Co. KG, 33607 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Schmeer","sequence":"additional","affiliation":[{"name":"PlasmidFactory GmbH & Co. KG, 33607 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Carlos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Piqueras 98, 3th Floor, 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8100-3876","authenticated-orcid":false,"given":"Guglielmo","family":"Verona","sequence":"additional","affiliation":[{"name":"Centre for Amyloidosis, UCL Medical School, Rowland Hill Street, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1238-9442","authenticated-orcid":false,"given":"Lydia","family":"Alvarez-Erviti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Piqueras 98, 3th Floor, 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/mds.25945","article-title":"The prevalence of Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"29","author":"Pringsheim","year":"2014","journal-title":"Mov. 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