{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T09:53:00Z","timestamp":1793267580030,"version":"4.5.0"},"reference-count":91,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UH3AR075336"],"award-info":[{"award-number":["UH3AR075336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UG3AR07336"],"award-info":[{"award-number":["UG3AR07336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UG3AR07336"],"award-info":[{"award-number":["UG3AR07336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UH3AR075336"],"award-info":[{"award-number":["UH3AR075336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UH3AR075336"],"award-info":[{"award-number":["UH3AR075336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UG3AR07336"],"award-info":[{"award-number":["UG3AR07336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UG3AR07336"],"award-info":[{"award-number":["UG3AR07336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UH3AR075336"],"award-info":[{"award-number":["UH3AR075336"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Protoc"],"published-print":{"date-parts":[[2023,11]]},"DOI":"10.1038\/s41596-023-00875-y","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T07:01:58Z","timestamp":1695279718000},"page":"3413-3459","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery"],"prefix":"10.1038","volume":"18","author":[{"given":"Trevor J.","family":"Gonzalez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-8868","authenticated-orcid":false,"given":"Aaron","family":"Mitchell-Dick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9211-259X","authenticated-orcid":false,"given":"Leo O.","family":"Blondel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco M.","family":"Fanous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Hull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel K.","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Moller-Tank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth M.","family":"Castellanos Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A.","family":"Piedrahita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5563-4877","authenticated-orcid":false,"given":"Aravind","family":"Asokan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"875_CR1","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.ymthe.2020.12.007","volume":"29","author":"JR Mendell","year":"2021","unstructured":"Mendell, J. R. et al. Current clinical applications of in vivo gene therapy with AAVs. Mol. Ther. 29, 464\u2013488 (2021).","journal-title":"Mol. Ther."},{"key":"875_CR2","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/d41573-021-00017-7","volume":"20","author":"DA Kuzmin","year":"2021","unstructured":"Kuzmin, D. A. et al. The clinical landscape for AAV gene therapies. Nat. Rev. Drug Discov. 20, 173\u2013174 (2021).","journal-title":"Nat. Rev. Drug Discov."},{"key":"875_CR3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nrg2988","volume":"12","author":"F Mingozzi","year":"2011","unstructured":"Mingozzi, F. & High, K. A. Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat. Rev. Genet 12, 341\u2013355 (2011).","journal-title":"Nat. Rev. Genet"},{"key":"875_CR4","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.neuron.2019.02.017","volume":"101","author":"E Hudry","year":"2019","unstructured":"Hudry, E. & Vandenberghe, L. H. Therapeutic AAV gene transfer to the nervous system: a clinical reality. Neuron 101, 839\u2013862 (2019).","journal-title":"Neuron"},{"key":"875_CR5","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nrd.2018.110","volume":"17","author":"BE Deverman","year":"2018","unstructured":"Deverman, B. E. et al. Gene therapy for neurological disorders: progress and prospects. Nat. Rev. Drug Discov. 17, 641\u2013659 (2018).","journal-title":"Nat. Rev. Drug Discov."},{"key":"875_CR6","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1001\/jamaneurol.2018.0233","volume":"75","author":"MS Rafii","year":"2018","unstructured":"Rafii, M. S. et al. Adeno-associated viral vector (serotype 2)-nerve growth factor for patients with Alzheimer disease: a randomized clinical trial. JAMA Neurol. 75, 834\u2013841 (2018).","journal-title":"JAMA Neurol."},{"key":"875_CR7","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","volume":"21","author":"C Li","year":"2020","unstructured":"Li, C. & Samulski, R. J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet 21, 255\u2013272 (2020).","journal-title":"Nat. Rev. Genet"},{"key":"875_CR8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.copbio.2019.01.002","volume":"60","author":"C Barnes","year":"2019","unstructured":"Barnes, C., Scheideler, O. & Schaffer, D. Engineering the AAV capsid to evade immune responses. Curr. Opin. Biotechnol. 60, 99\u2013103 (2019).","journal-title":"Curr. Opin. Biotechnol."},{"key":"875_CR9","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nrg3742","volume":"15","author":"MA Kotterman","year":"2014","unstructured":"Kotterman, M. A. & Schaffer, D. V. Engineering adeno-associated viruses for clinical gene therapy. Nat. Rev. Genet. 15, 445\u2013451 (2014).","journal-title":"Nat. Rev. Genet."},{"key":"875_CR10","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","volume":"18","author":"D Wang","year":"2019","unstructured":"Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358\u2013378 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"875_CR11","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.molmed.2022.01.003","volume":"28","author":"S Zolotukhin","year":"2022","unstructured":"Zolotukhin, S. & Vandenberghe, L. H. AAV capsid design: a Goldilocks challenge. Trends Mol. Med 28, 183\u2013193 (2022).","journal-title":"Trends Mol. Med"},{"key":"875_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33745-4","volume":"13","author":"TJ Gonzalez","year":"2022","unstructured":"Gonzalez, T. J. et al. Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing. Nat. Commun. 13, 5947 (2022).","journal-title":"Nat. Commun."},{"key":"875_CR13","doi-asserted-by":"publisher","first-page":"e00976-20","DOI":"10.1128\/JVI.00976-20","volume":"94","author":"LP Havlik","year":"2020","unstructured":"Havlik, L. P. et al. Coevolution of adeno-associated virus capsid antigenicity and tropism through a structure-guided approach. J. Virol. 94, e00976-20 (2020).","journal-title":"J. Virol."},{"key":"875_CR14","doi-asserted-by":"publisher","first-page":"E4812","DOI":"10.1073\/pnas.1704766114","volume":"114","author":"LV Tse","year":"2017","unstructured":"Tse, L. V. et al. Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion. Proc. Natl Acad. Sci. USA 114, E4812\u2013E4821 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"875_CR15","doi-asserted-by":"publisher","first-page":"e0058721","DOI":"10.1128\/JVI.00587-21","volume":"95","author":"LP Havlik","year":"2021","unstructured":"Havlik, L. P. et al. Receptor switching in newly evolved adeno-associated viruses. J. Virol. 95, e0058721 (2021).","journal-title":"J. Virol."},{"key":"875_CR16","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.ymthe.2017.10.017","volume":"26","author":"BH Albright","year":"2018","unstructured":"Albright, B. H. et al. Mapping the structural determinants required for AAVrh.10 transport across the blood-brain barrier. Mol. Ther. 26, 510\u2013523 (2018).","journal-title":"Mol. Ther."},{"key":"875_CR17","doi-asserted-by":"publisher","first-page":"3976","DOI":"10.1128\/JVI.02951-14","volume":"89","author":"G Murlidharan","year":"2015","unstructured":"Murlidharan, G. et al. Unique glycan signatures regulate adeno-associated virus tropism in the developing brain. J. Virol. 89, 3976\u20133987 (2015).","journal-title":"J. Virol."},{"key":"875_CR18","doi-asserted-by":"publisher","first-page":"13206","DOI":"10.1128\/JVI.02109-13","volume":"87","author":"S Shen","year":"2013","unstructured":"Shen, S. et al. Multiple roles for sialylated glycans in determining the cardiopulmonary tropism of adeno-associated virus 4. J. Virol. 87, 13206\u201313213 (2013).","journal-title":"J. Virol."},{"key":"875_CR19","doi-asserted-by":"publisher","first-page":"27053","DOI":"10.1073\/pnas.1910061116","volume":"116","author":"M Davidsson","year":"2019","unstructured":"Davidsson, M. et al. A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism. Proc. Natl Acad. Sci. USA 116, 27053\u201327062 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"875_CR20","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nbt.3440","volume":"34","author":"BE Deverman","year":"2016","unstructured":"Deverman, B. E. et al. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat. Biotechnol. 34, 204\u2013209 (2016).","journal-title":"Nat. Biotechnol."},{"key":"875_CR21","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.ymthe.2018.01.018","volume":"26","author":"J Hordeaux","year":"2018","unstructured":"Hordeaux, J. et al. The neurotropic properties of AAV-PHP.B are limited to C57BL\/6J mice. Mol. Ther. 26, 664\u2013668 (2018).","journal-title":"Mol. Ther."},{"key":"875_CR22","doi-asserted-by":"publisher","first-page":"10408","DOI":"10.1128\/JVI.01155-12","volume":"86","author":"S Shen","year":"2012","unstructured":"Shen, S. et al. Glycan binding avidity determines the systemic fate of adeno-associated virus type 9. J. Virol. 86, 10408\u201310417 (2012).","journal-title":"J. Virol."},{"key":"875_CR23","doi-asserted-by":"publisher","first-page":"28814","DOI":"10.1074\/jbc.M113.482380","volume":"288","author":"S Shen","year":"2013","unstructured":"Shen, S. et al. Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency. J. Biol. Chem. 288, 28814\u201328823 (2013).","journal-title":"J. Biol. Chem."},{"key":"875_CR24","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nbt.1599","volume":"28","author":"A Asokan","year":"2010","unstructured":"Asokan, A. et al. Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Nat. Biotechnol. 28, 79\u201382 (2010).","journal-title":"Nat. Biotechnol."},{"key":"875_CR25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.coviro.2016.05.001","volume":"18","author":"VJ Madigan","year":"2016","unstructured":"Madigan, V. J. & Asokan, A. Engineering AAV receptor footprints for gene therapy. Curr. Opin. Virol. 18, 89\u201396 (2016).","journal-title":"Curr. Opin. Virol."},{"key":"875_CR26","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1089\/hum.2016.130","volume":"28","author":"AF Tarantal","year":"2017","unstructured":"Tarantal, A. F. et al. Systemic and persistent muscle gene expression in rhesus monkeys with a liver de-targeted adeno-associated virus vector. Hum. Gene Ther. 28, 385\u2013391 (2017).","journal-title":"Hum. Gene Ther."},{"key":"875_CR27","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/mt.2015.134","volume":"24","author":"C Li","year":"2016","unstructured":"Li, C. et al. Development of patient-specific AAV vectors after neutralizing antibody selection for enhanced muscle gene transfer. Mol. Ther. 24, 53\u201365 (2016).","journal-title":"Mol. Ther."},{"key":"875_CR28","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1126\/science.aaw2900","volume":"366","author":"PJ Ogden","year":"2019","unstructured":"Ogden, P. J. et al. Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design. Science 366, 1139\u20131143 (2019).","journal-title":"Science"},{"key":"875_CR29","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/s41587-020-00793-4","volume":"39","author":"DH Bryant","year":"2021","unstructured":"Bryant, D. H. et al. Deep diversification of an AAV capsid protein by machine learning. Nat. Biotechnol. 39, 691\u2013696 (2021).","journal-title":"Nat. Biotechnol."},{"key":"875_CR30","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.neuron.2016.09.021","volume":"92","author":"DG Tervo","year":"2016","unstructured":"Tervo, D. G. et al. A designer AAV variant permits efficient retrograde access to projection neurons. Neuron 92, 372\u2013382 (2016).","journal-title":"Neuron"},{"key":"875_CR31","doi-asserted-by":"publisher","first-page":"e01394-18","DOI":"10.1128\/JVI.01394-18","volume":"93","author":"A Jose","year":"2019","unstructured":"Jose, A. et al. High-resolution structural characterization of a new adeno-associated virus serotype 5 antibody epitope toward engineering antibody-resistant recombinant gene delivery vectors. J. Virol. 93, e01394-18 (2019).","journal-title":"J. Virol."},{"key":"875_CR32","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.tim.2021.09.005","volume":"30","author":"NL Meyer","year":"2022","unstructured":"Meyer, N. L. & Chapman, M. S. Adeno-associated virus (AAV) cell entry: structural insights. Trends Microbiol 30, 432\u2013451 (2022).","journal-title":"Trends Microbiol"},{"key":"875_CR33","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1089\/vim.2020.0022","volume":"34","author":"SN Emmanuel","year":"2021","unstructured":"Emmanuel, S. N. et al. Parvovirus capsid-antibody complex structures reveal conservation of antigenic epitopes across the family. Viral Immunol. 34, 3\u201317 (2021).","journal-title":"Viral Immunol."},{"key":"875_CR34","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1128\/JVI.02710-14","volume":"89","author":"YS Tseng","year":"2015","unstructured":"Tseng, Y. S. et al. Adeno-associated virus serotype 1 (AAV1)- and AAV5-antibody complex structures reveal evolutionary commonalities in parvovirus antigenic reactivity. J. Virol. 89, 1794\u20131808 (2015).","journal-title":"J. Virol."},{"key":"875_CR35","doi-asserted-by":"publisher","first-page":"e0124921","DOI":"10.1128\/JVI.01249-21","volume":"95","author":"M Mietzsch","year":"2021","unstructured":"Mietzsch, M. et al. Structural study of Aavrh.10 receptor and antibody interactions. J. Virol. 95, e0124921 (2021).","journal-title":"J. Virol."},{"key":"875_CR36","doi-asserted-by":"publisher","first-page":"e0125121","DOI":"10.1128\/JVI.01251-21","volume":"96","author":"SN Emmanuel","year":"2022","unstructured":"Emmanuel, S. N. et al. Structurally mapping antigenic epitopes of adeno-associated virus 9: development of antibody escape variants. J. Virol. 96, e0125121 (2022).","journal-title":"J. Virol."},{"key":"875_CR37","doi-asserted-by":"publisher","first-page":"3649","DOI":"10.1002\/1873-3468.13699","volume":"593","author":"S Hemmi","year":"2019","unstructured":"Hemmi, S. & Spindler, K. R. Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host. FEBS Lett. 593, 3649\u20133659 (2019).","journal-title":"FEBS Lett."},{"key":"875_CR38","doi-asserted-by":"publisher","first-page":"9398","DOI":"10.1128\/JVI.00954-09","volume":"83","author":"LE Gralinski","year":"2009","unstructured":"Gralinski, L. E. et al. Mouse adenovirus type 1-induced breakdown of the blood-brain barrier. J. Virol. 83, 9398\u20139410 (2009).","journal-title":"J. Virol."},{"key":"875_CR39","doi-asserted-by":"publisher","first-page":"7674","DOI":"10.1128\/jvi.69.12.7674-7681.1995","volume":"69","author":"JD Guida","year":"1995","unstructured":"Guida, J. D. et al. Mouse adenovirus type 1 causes a fatal hemorrhagic encephalomyelitis in adult C57BL\/6 but not BALB\/c mice. J. Virol. 69, 7674\u20137681 (1995).","journal-title":"J. Virol."},{"key":"875_CR40","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.virol.2005.06.021","volume":"340","author":"JB Weinberg","year":"2005","unstructured":"Weinberg, J. B. et al. Acute respiratory infection with mouse adenovirus type 1. Virology 340, 245\u2013254 (2005).","journal-title":"Virology"},{"key":"875_CR41","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1128\/JVI.72.2.1219-1223.1998","volume":"72","author":"AE Kajon","year":"1998","unstructured":"Kajon, A. E., Brown, C. C. & Spindler, K. R. Distribution of mouse adenovirus type 1 in intraperitoneally and intranasally infected adult outbred mice. J. Virol. 72, 1219\u20131223 (1998).","journal-title":"J. Virol."},{"key":"875_CR42","doi-asserted-by":"publisher","first-page":"5749","DOI":"10.1128\/JVI.02281-08","volume":"83","author":"B Klempa","year":"2009","unstructured":"Klempa, B. et al. A novel cardiotropic murine adenovirus representing a distinct species of mastadenoviruses. J. Virol. 83, 5749\u20135759 (2009).","journal-title":"J. Virol."},{"key":"875_CR43","doi-asserted-by":"publisher","first-page":"e01412","DOI":"10.1128\/JVI.01412-16","volume":"91","author":"SL Ashley","year":"2017","unstructured":"Ashley, S. L. et al. Matrix metalloproteinase activity in infections by an encephalitic virus, mouse adenovirus type 1. J. Virol. 91, e01412\u2013e01416 (2017).","journal-title":"J. Virol."},{"key":"875_CR44","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1007\/s00335-011-9368-9","volume":"23","author":"MT Stier","year":"2012","unstructured":"Stier, M. T. & Spindler, K. R. Polymorphisms in Ly6 genes in Msq1 encoding susceptibility to mouse adenovirus type 1. Mamm. Genome 23, 250\u2013258 (2012).","journal-title":"Mamm. Genome"},{"key":"875_CR45","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/nbt1182","volume":"24","author":"N Maheshri","year":"2006","unstructured":"Maheshri, N. et al. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat. Biotechnol. 24, 198\u2013204 (2006).","journal-title":"Nat. Biotechnol."},{"key":"875_CR46","doi-asserted-by":"publisher","first-page":"5887","DOI":"10.1128\/JVI.00254-08","volume":"82","author":"D Grimm","year":"2008","unstructured":"Grimm, D. et al. In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated viruses. J. Virol. 82, 5887\u20135911 (2008).","journal-title":"J. Virol."},{"key":"875_CR47","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/mt.2009.292","volume":"18","author":"SJ Gray","year":"2010","unstructured":"Gray, S. J. et al. Directed evolution of a novel adeno-associated virus (AAV) vector that crosses the seizure-compromised blood-brain barrier (BBB). Mol. Ther. 18, 570\u2013578 (2010).","journal-title":"Mol. Ther."},{"key":"875_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19230-w","volume":"11","author":"J Weinmann","year":"2020","unstructured":"Weinmann, J. et al. Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants. Nat. Commun. 11, 5432 (2020).","journal-title":"Nat. Commun."},{"key":"875_CR49","doi-asserted-by":"publisher","first-page":"4919","DOI":"10.1016\/j.cell.2021.08.028","volume":"184","author":"M Tabebordbar","year":"2021","unstructured":"Tabebordbar, M. et al. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell 184, 4919\u20134938.e22 (2021).","journal-title":"Cell"},{"key":"875_CR50","doi-asserted-by":"publisher","first-page":"eabn4704","DOI":"10.1126\/sciadv.abn4704","volume":"8","author":"J El Andari","year":"2022","unstructured":"El Andari, J. et al. Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders. Sci. Adv. 8, eabn4704 (2022).","journal-title":"Sci. Adv."},{"key":"875_CR51","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.omtm.2020.12.006","volume":"20","author":"M Nonnenmacher","year":"2021","unstructured":"Nonnenmacher, M. et al. Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning. Mol. Ther. Methods Clin. Dev. 20, 366\u2013378 (2021).","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"875_CR52","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/mt.2011.177","volume":"20","author":"K Rapti","year":"2012","unstructured":"Rapti, K. et al. Neutralizing antibodies against AAV serotypes 1, 2, 6, and 9 in sera of commonly used animal models. Mol. Ther. 20, 73\u201383 (2012).","journal-title":"Mol. Ther."},{"key":"875_CR53","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1038\/nprot.2015.103","volume":"10","author":"MJ Smola","year":"2015","unstructured":"Smola, M. J. et al. Selective 2\u2032-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for direct, versatile and accurate RNA structure analysis. Nat. Protoc. 10, 1643\u20131669 (2015).","journal-title":"Nat. Protoc."},{"key":"875_CR54","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1111\/bph.15193","volume":"177","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. Br. J. Pharm. 177, 3617\u20133624 (2020).","journal-title":"Br. J. Pharm."},{"key":"875_CR55","doi-asserted-by":"publisher","first-page":"D809","DOI":"10.1093\/nar\/gkaa1096","volume":"49","author":"D Montiel-Garcia","year":"2021","unstructured":"Montiel-Garcia, D. et al. VIPERdb v3.0: a structure-based data analytics platform for viral capsids. Nucleic Acids Res. 49, D809\u2013D816 (2021).","journal-title":"Nucleic Acids Res."},{"key":"875_CR56","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"J Jumper","year":"2021","unstructured":"Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583\u2013589 (2021).","journal-title":"Nature"},{"key":"875_CR57","doi-asserted-by":"publisher","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","volume":"50","author":"M Varadi","year":"2022","unstructured":"Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439\u2013D444 (2022).","journal-title":"Nucleic Acids Res."},{"key":"875_CR58","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2014a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612 (2004).","journal-title":"J. Comput. Chem."},{"key":"875_CR59","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P. et al. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"875_CR60","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1038\/nprot.2006.207","volume":"1","author":"JC Grieger","year":"2006","unstructured":"Grieger, J. C., Choi, V. W. & Samulski, R. J. Production and characterization of adeno-associated viral vectors. Nat. Protoc. 1, 1412\u20131428 (2006).","journal-title":"Nat. Protoc."},{"key":"875_CR61","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.omtm.2019.11.014","volume":"17","author":"PF Schmit","year":"2020","unstructured":"Schmit, P. F. et al. Cross-packaging and capsid mosaic formation in multiplexed AAV libraries. Mol. Ther. Methods Clin. Dev. 17, 107\u2013121 (2020).","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"875_CR62","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1128\/JVI.72.3.2224-2232.1998","volume":"72","author":"X Xiao","year":"1998","unstructured":"Xiao, X., Li, J. & Samulski, R. J. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J. Virol. 72, 2224\u20132232 (1998).","journal-title":"J. Virol."},{"key":"875_CR63","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3390\/v11040362","volume":"11","author":"M Mietzsch","year":"2019","unstructured":"Mietzsch, M., Penzes, J. J. & Agbandje-McKenna, M. Twenty-five years of structural parvovirology. Viruses 11, 362 (2019).","journal-title":"Viruses"},{"key":"875_CR64","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/fimmu.2014.00009","volume":"5","author":"YS Tseng","year":"2014","unstructured":"Tseng, Y. S. & Agbandje-McKenna, M. Mapping the AAV capsid host antibody response toward the development of second generation gene delivery vectors. Front. Immunol. 5, 9 (2014).","journal-title":"Front. Immunol."},{"key":"875_CR65","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41596-018-0097-3","volume":"14","author":"RC Challis","year":"2019","unstructured":"Challis, R. C. et al. Systemic AAV vectors for widespread and targeted gene delivery in rodents. Nat. Protoc. 14, 379\u2013414 (2019).","journal-title":"Nat. Protoc."},{"key":"875_CR66","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nmeth.1318","volume":"6","author":"DG Gibson","year":"2009","unstructured":"Gibson, D. G. et al. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods 6, 343\u2013345 (2009).","journal-title":"Nat. Methods"},{"key":"875_CR67","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/s41593-021-00969-4","volume":"25","author":"D Goertsen","year":"2022","unstructured":"Goertsen, D. et al. AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset. Nat. Neurosci. 25, 106\u2013115 (2022).","journal-title":"Nat. Neurosci."},{"key":"875_CR68","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/mt.2015.3","volume":"23","author":"M Nonnenmacher","year":"2015","unstructured":"Nonnenmacher, M. et al. High capsid-genome correlation facilitates creation of AAV libraries for directed evolution. Mol. Ther. 23, 675\u2013682 (2015).","journal-title":"Mol. Ther."},{"key":"875_CR69","doi-asserted-by":"publisher","first-page":"11556","DOI":"10.1128\/JVI.01536-06","volume":"80","author":"L Govindasamy","year":"2006","unstructured":"Govindasamy, L. et al. Structurally mapping the diverse phenotype of adeno-associated virus serotype 4. J. Virol. 80, 11556\u201311570 (2006).","journal-title":"J. Virol."},{"key":"875_CR70","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.omtm.2020.10.001","volume":"19","author":"M Mietzsch","year":"2020","unstructured":"Mietzsch, M. et al. Characterization of AAV-specific affinity ligands: consequences for vector purification and development strategies. Mol. Ther. Methods Clin. Dev. 19, 362\u2013373 (2020).","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"875_CR71","doi-asserted-by":"publisher","first-page":"5219","DOI":"10.1128\/JVI.00161-16","volume":"90","author":"LY Huang","year":"2016","unstructured":"Huang, L. Y. et al. Characterization of the adeno-associated virus 1 and 6 sialic acid binding site. J. Virol. 90, 5219\u20135230 (2016).","journal-title":"J. Virol."},{"key":"875_CR72","doi-asserted-by":"publisher","first-page":"e44707","DOI":"10.7554\/eLife.44707","volume":"8","author":"NL Meyer","year":"2019","unstructured":"Meyer, N. L. et al. Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR. Elife 8, e44707 (2019).","journal-title":"Elife"},{"key":"875_CR73","doi-asserted-by":"publisher","first-page":"e01980-16","DOI":"10.1128\/JVI.01980-16","volume":"91","author":"LF Earley","year":"2017","unstructured":"Earley, L. F. et al. Adeno-associated virus (AAV) assembly-activating protein is not an essential requirement for capsid assembly of AAV serotypes 4, 5, and 11. J. Virol. 91, e01980-16 (2017).","journal-title":"J. Virol."},{"key":"875_CR74","doi-asserted-by":"publisher","first-page":"2528","DOI":"10.1128\/JVI.79.4.2528-2540.2005","volume":"79","author":"S Bleker","year":"2005","unstructured":"Bleker, S., Sonntag, F. & Kleinschmidt, J. A. Mutational analysis of narrow pores at the fivefold symmetry axes of adeno-associated virus type 2 capsids reveals a dual role in genome packaging and activation of phospholipase A2 activity. J. Virol. 79, 2528\u20132540 (2005).","journal-title":"J. Virol."},{"key":"875_CR75","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1128\/JVI.80.2.810-820.2006","volume":"80","author":"S Bleker","year":"2006","unstructured":"Bleker, S., Pawlita, M. & Kleinschmidt, J. A. Impact of capsid conformation and Rep-capsid interactions on adeno-associated virus type 2 genome packaging. J. Virol. 80, 810\u2013820 (2006).","journal-title":"J. Virol."},{"key":"875_CR76","doi-asserted-by":"publisher","first-page":"7833","DOI":"10.1128\/JVI.00580-07","volume":"81","author":"JC Grieger","year":"2007","unstructured":"Grieger, J. C. et al. Surface-exposed adeno-associated virus Vp1-NLS capsid fusion protein rescues infectivity of noninfectious wild-type Vp2\/Vp3 and Vp3-only capsids but not that of fivefold pore mutant virions. J. Virol. 81, 7833\u20137843 (2007).","journal-title":"J. Virol."},{"key":"875_CR77","doi-asserted-by":"publisher","first-page":"5296","DOI":"10.1128\/JVI.79.9.5296-5303.2005","volume":"79","author":"S Kronenberg","year":"2005","unstructured":"Kronenberg, S. et al. A conformational change in the adeno-associated virus type 2 capsid leads to the exposure of hidden VP1 N termini. J. Virol. 79, 5296\u20135303 (2005).","journal-title":"J. Virol."},{"key":"875_CR78","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/mt.2011.3","volume":"19","author":"NM Kotchey","year":"2011","unstructured":"Kotchey, N. M. et al. A potential role of distinctively delayed blood clearance of recombinant adeno-associated virus serotype 9 in robust cardiac transduction. Mol. Ther. 19, 1079\u20131089 (2011).","journal-title":"Mol. Ther."},{"key":"875_CR79","doi-asserted-by":"publisher","first-page":"e54","DOI":"10.1038\/mtna.2012.46","volume":"1","author":"J Judd","year":"2012","unstructured":"Judd, J. et al. Random insertion of mCherry into VP3 domain of adeno-associated virus yields fluorescent capsids with no loss of infectivity. Mol. Ther. Nucleic Acids 1, e54 (2012).","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"875_CR80","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.omtm.2020.11.004","volume":"19","author":"CB Jackson","year":"2020","unstructured":"Jackson, C. B. et al. AAV vectors engineered to target insulin receptor greatly enhance intramuscular gene delivery. Mol. Ther. Methods Clin. Dev. 19, 496\u2013506 (2020).","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"875_CR81","doi-asserted-by":"publisher","first-page":"6947","DOI":"10.1128\/JVI.07232-11","volume":"86","author":"MA DiMattia","year":"2012","unstructured":"DiMattia, M. A. et al. Structural insight into the unique properties of adeno-associated virus serotype 9. J. Virol. 86, 6947\u20136958 (2012).","journal-title":"J. Virol."},{"key":"875_CR82","doi-asserted-by":"publisher","first-page":"e0033522","DOI":"10.1128\/jvi.00335-22","volume":"96","author":"M Mietzsch","year":"2022","unstructured":"Mietzsch, M. et al. Characterization of the serpentine adeno-associated virus (SAAV) capsid structure: receptor interactions and antigenicity. J. Virol. 96, e0033522 (2022).","journal-title":"J. Virol."},{"key":"875_CR83","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1038\/mt.2009.155","volume":"17","author":"W Li","year":"2009","unstructured":"Li, W. et al. Generation of novel AAV variants by directed evolution for improved CFTR delivery to human ciliated airway epithelium. Mol. Ther. 17, 2067\u20132077 (2009).","journal-title":"Mol. Ther."},{"key":"875_CR84","doi-asserted-by":"publisher","first-page":"9111","DOI":"10.1128\/JVI.00622-13","volume":"87","author":"BL Gurda","year":"2013","unstructured":"Gurda, B. L. et al. Capsid antibodies to different adeno-associated virus serotypes bind common regions. J. Virol. 87, 9111\u20139124 (2013).","journal-title":"J. Virol."},{"key":"875_CR85","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1038\/mt.2011.22","volume":"19","author":"N Pulicherla","year":"2011","unstructured":"Pulicherla, N. et al. Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer. Mol. Ther. 19, 1070\u20131078 (2011).","journal-title":"Mol. Ther."},{"key":"875_CR86","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1128\/JVI.02503-14","volume":"89","author":"S Afione","year":"2015","unstructured":"Afione, S. et al. Identification and mutagenesis of the adeno-associated virus 5 sialic acid binding region. J. Virol. 89, 1660\u20131672 (2015).","journal-title":"J. Virol."},{"key":"875_CR87","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.virol.2010.03.027","volume":"403","author":"TF Lerch","year":"2010","unstructured":"Lerch, T. F., Xie, Q. & Chapman, M. S. The structure of adeno-associated virus serotype 3B (AAV-3B): insights into receptor binding and immune evasion. Virology 403, 26\u201336 (2010).","journal-title":"Virology"},{"key":"875_CR88","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1089\/hum.2011.139","volume":"23","author":"M Naumer","year":"2012","unstructured":"Naumer, M. et al. Development and validation of novel AAV2 random libraries displaying peptides of diverse lengths and at diverse capsid positions. Hum. Gene Ther. 23, 492\u2013507 (2012).","journal-title":"Hum. Gene Ther."},{"key":"875_CR89","doi-asserted-by":"publisher","first-page":"e23101","DOI":"10.1371\/journal.pone.0023101","volume":"6","author":"S Michelfelder","year":"2011","unstructured":"Michelfelder, S. et al. Peptide ligands incorporated into the threefold spike capsid domain to re-direct gene transduction of AAV8 and AAV9 in vivo. PLoS ONE 6, e23101 (2011).","journal-title":"PLoS ONE"},{"key":"875_CR90","doi-asserted-by":"publisher","first-page":"5178","DOI":"10.1128\/JVI.02721-07","volume":"82","author":"N DiPrimio","year":"2008","unstructured":"DiPrimio, N. et al. Surface loop dynamics in adeno-associated virus capsid assembly. J. Virol. 82, 5178\u20135189 (2008).","journal-title":"J. Virol."},{"key":"875_CR91","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1021\/cb3000265","volume":"7","author":"ED Horowitz","year":"2012","unstructured":"Horowitz, E. D., Finn, M. G. & Asokan, A. Tyrosine cross-linking reveals interfacial dynamics in adeno-associated viral capsids during infection. ACS Chem. Biol. 7, 1059\u20131066 (2012).","journal-title":"ACS Chem. Biol."}],"container-title":["Nature Protocols"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41596-023-00875-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41596-023-00875-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41596-023-00875-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T11:08:31Z","timestamp":1699268911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41596-023-00875-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,21]]},"references-count":91,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["875"],"URL":"https:\/\/doi.org\/10.1038\/s41596-023-00875-y","relation":{},"ISSN":["1754-2189","1750-2799"],"issn-type":[{"value":"1754-2189","type":"print"},{"value":"1750-2799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,21]]},"assertion":[{"value":"21 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"T.J.G. and A.A. have filed patent applications on the subject matter of this paper. A.A. is a co-founder at StrideBio and TorqueBio and serves on the advisory boards of Atsena Therapeutics, Isolere Bio, Mammoth Bio, Ring Therapeutics and Kriya Therapeutics. S.M.-T. is a current employee of Regeneron Pharmaceuticals. R.M.C.R. is a current employee of Kriya Therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}