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Promising vector candidates were identified by screening large pools of adeno-associated virus (AAV) mutants in small animal models. However, it became apparent that targeted AAV mutants isolated from rodents may not function in humans as the tropism of individual AAV mutants can differ between species. To identify novel vascular-targeted AAV capsid mutants suitable for treating human patients, we generated a set of AAV2 display peptide libraries and screened them in the common marmoset, a non-human primate. To evaluate the impact of different AAV library production methods, progress of the screening process was monitored by next generation sequencing. Particle distribution and enrichment was compared between different AAV libraries and selection rounds. We observed enrichment of AAV variants in the brain and other well-perfused organs (lung, heart, kidney) potentially mediated by high capsid affinity for the vascular endothelium in general. In vitro experiments on primary human microvascular endothelial cells isolated from a set of different organs (brain, heart, lung, liver, kidney and spleen) confirmed superior transduction of a selected AAV variant displaying the \u201cDWP\u201d amino acid sequence motif compared to natural AAV serotypes 1\u20139.<\/jats:p>","DOI":"10.1038\/s41434-025-00563-4","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T09:46:25Z","timestamp":1755855985000},"page":"529-541","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of AAV variants with improved transduction of human vascular endothelial cells by screening AAV capsid libraries in non-human primates"],"prefix":"10.1038","volume":"32","author":[{"given":"Maria","family":"Stamataki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"L\u00fcschow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Schlumbohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-7709","authenticated-orcid":false,"given":"Malik","family":"Alawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Lunding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Trepel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4510-9718","authenticated-orcid":false,"given":"Markus","family":"Schwaninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5435-7182","authenticated-orcid":false,"given":"Jakob","family":"K\u00f6rbelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"563_CR1","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.1016\/j.ymthe.2022.09.015","volume":"30","author":"A Pupo","year":"2022","unstructured":"Pupo A, Fernandez A, Low SH, Francois A, Suarez-Amaran L, Samulski RJ. 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All other authors declare that there is no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The animal experiment was conducted in accordance with the German Law for the Protection of Animals and the European Union\u2019s legislation on the protection of animals used for scientific purpose (EU directive 2010\/63\/EU). The Ethical application and the study protocol were reviewed by the Lower Saxony ethical committee for animal experiments (\u00a7 15 committee) and by the ethical committee and animal welfare officer of Neu Encepharm. The responsible local authorities (Nieders\u00e4chsisches Landesamt f\u00fcr Verbraucherschutz und Lebensmittelsicherheit, Lower Saxony, Germany) approved the ethical application under the registration number 14\/1583. Human primary cells were obtained from ScienCell. All ScienCell Research Laboratories human cells are sourced within the USA under protocols that have obtained Institutional Review Board (IRB) approval, governed by Title 45 of the Code of Federal Regulations (CFR) Part 46. IRBs are federally empowered by the US Food and Drug Administration (FDA) and the Department of Health and Human Services who authorize and task them to review, modify, approve or disapprove proposed research involving human subjects under the regulations of 45 CFR Part 46. Fundamental to obtaining IRB approval is that the important ethical tenets outlined in the Belmont Report (Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research) are adhered to.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}