{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:38:05Z","timestamp":1792719485963,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25am0521002"],"award-info":[{"award-number":["JP25am0521002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibody delivery across the blood\u2013brain barrier (BBB) remains challenging. We combined phage display with next-generation sequencing-guided clone sequence-diverse selection to identify transferrin receptor 1 (TfR1)-binding VHH antibodies. Following alpaca immunization with human and rat TfR1, representative clones from distinct phylogenetic groups were screened for human\/mouse cross-reactivity. Three clones (A1, Y11 and Z1) were reformatted as human Fc-mutant fusion proteins and characterized by ELISA, flow cytometry and fluorescence imaging. All three clones recognized human and mouse TfR1, with ELISA EC50\u00a0&amp;gt;\u2009100\u00a0nM. After intravenous administration in mice, clone Y11 showed sustained brain-associated fluorescence up to 48\u00a0h, whereas A1 showed an initially high signal that progressively declined. Fluorescent microscopy revealed preferential localization of Y11 to NeuN-positive neuronal regions, whereas A1 to lectin-positive vascular structures, indicating distinct brain localization profiles among the isolated clones. These findings identify cross-reactive TfR1-targeting VHHs with distinct brain-localization profiles and potential utility as platforms for compartment-selective CNS drug delivery.<\/jats:p>","DOI":"10.1093\/jb\/mvag070","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:46:28Z","timestamp":1791459988000},"source":"Crossref","is-referenced-by-count":0,"title":["NGS-guided discovery of cross-reactive TfR1 VHH antibodies with distinct brain localization profiles"],"prefix":"10.1093","author":[{"given":"Muhammad Feisal","family":"Jatnika","sequence":"first","affiliation":[{"name":"Graduate School of Science and Engineering, Kagoshima University , 1-21-35 Korimoto, Kagoshima City, Kagoshima , 890-0065,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaki","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Graduate School of Science and Engineering, Kagoshima University , 1-21-35 Korimoto, Kagoshima City, Kagoshima , 890-0065,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakana","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Graduate School of Science and Engineering, Kagoshima University , 1-21-35 Korimoto, Kagoshima City, Kagoshima , 890-0065,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdur","family":"Rafique","sequence":"additional","affiliation":[{"name":"Graduate School of Science and Engineering, Kagoshima University , 1-21-35 Korimoto, Kagoshima City, Kagoshima , 890-0065,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-5070","authenticated-orcid":false,"given":"Yuji","family":"Ito","sequence":"additional","affiliation":[{"name":"Graduate School of Science and Engineering, Kagoshima University , 1-21-35 Korimoto, Kagoshima City, Kagoshima , 890-0065,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"2026102221020301800_ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-019-0592-z","article-title":"Development of therapeutic antibodies for the treatment of diseases","volume":"27","author":"Lu","year":"2020","journal-title":"J. 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