{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:51:14Z","timestamp":1790247074100,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T00:00:00Z","timestamp":1447286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G019314N"],"award-info":[{"award-number":["G019314N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G1000709"],"award-info":[{"award-number":["G1000709"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the success of viral vector technology in the transduction of the central nervous system in both preclinical research and gene therapy, its potential in neurogastroenterological research remains largely unexploited. This study asked whether and to what extent myenteric and submucosal neurons in the ileum and distal colon of the mouse were transduced after neonatal systemic delivery of recombinant adeno\u2010associated viral vectors (<jats:styled-content style=\"fixed-case\">AAVs<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were intravenously injected at postnatal day one with <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content> pseudotypes <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>8 or <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>9 carrying a cassette encoding enhanced green fluorescent protein (<jats:styled-content style=\"fixed-case\">eGFP<\/jats:styled-content>) as a reporter under the control of a cytomegalovirus promoter. At postnatal day 35, transduction of the myenteric and submucosal plexuses of the ileum and distal colon was evaluated in whole\u2010mount preparations, using immunohistochemistry to neurochemically identify transduced enteric neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The pseudotypes <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>8 and <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>9 showed equal potential in transducing the enteric nervous system (<jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content>), with 25\u201330% of the neurons expressing <jats:styled-content style=\"fixed-case\">eGFP<\/jats:styled-content>. However, the percentage of <jats:styled-content style=\"fixed-case\">eGFP<\/jats:styled-content>\u2010expressing colonic submucosal neurons was significantly lower. Neurochemical analysis showed that all enteric neuron subtypes, but not glia, expressed the reporter protein. Intrinsic sensory neurons were most efficiently transduced as nearly 80% of calcitonin gene\u2010related peptide\u2010positive neurons expressed the transgene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>The pseudotypes <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>8 and <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>9 can be employed for gene delivery to both the myenteric and the submucosal plexus, although the transduction efficiency in the latter is region\u2010dependent. These findings open perspectives for novel preclinical applications aimed at manipulating and imaging the <jats:styled-content style=\"fixed-case\">ENS<\/jats:styled-content> in the short term, and in gene therapy in the longer term.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12724","type":"journal-article","created":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T01:44:46Z","timestamp":1447379086000},"page":"299-305","source":"Crossref","is-referenced-by-count":33,"title":["Proof\u2010of\u2010concept: neonatal intravenous injection of adeno\u2010associated virus vectors results in successful transduction of myenteric and submucosal neurons in the mouse small and large intestine"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9976-2889","authenticated-orcid":false,"given":"R.","family":"Buckinx","sequence":"first","affiliation":[{"name":"Laboratory of Cell Biology and Histology Department of Veterinary Sciences University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Van Remoortel","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology Department of Veterinary Sciences University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Gijsbers","sequence":"additional","affiliation":[{"name":"Laboratory for Viral Vector Technology &amp; Gene Therapy Department of Pharmaceutical and Pharmacological Sciences KU Leuven Leuven Belgium"},{"name":"Leuven Viral Vector Core KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. N.","family":"Waddington","sequence":"additional","affiliation":[{"name":"Gene Transfer Technology Group Institute for Women's Health University College London London UK"},{"name":"Wits\/SAMRC Antiviral Gene Therapy Research Unit Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010P.","family":"Timmermans","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology Department of Veterinary Sciences University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.09.014"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00076"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652311795684759"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-182311"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00042"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00081"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.179"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-2012-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-011-0862-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2007.00931.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-2012-8"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.7"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-269092"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01155-12"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1372"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3738"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050565"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-008-0684-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-009-0773-2"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.12724","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.12724","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T17:55:44Z","timestamp":1696182944000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.12724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,12]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1111\/nmo.12724"],"URL":"https:\/\/doi.org\/10.1111\/nmo.12724","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,12]]}}}