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To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ad5). Patchy dendrimers bound to the surface of Ad5 formed a synthetic polymer corona that greatly altered various host interactions of Ad5 as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ad5 to blood coagulation factor X, one of the most critical virus\u2013host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ad5 with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications.<\/jats:p>","DOI":"10.1021\/acsnano.9b01484","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T12:22:46Z","timestamp":1563538966000},"page":"8749-8759","source":"Crossref","is-referenced-by-count":29,"title":["Patchy\nAmphiphilic Dendrimers Bind Adenovirus and\nControl Its Host Interactions and in Vivo Distribution"],"prefix":"10.1021","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-4982","authenticated-orcid":true,"given":"Yuzhou","family":"Wu","sequence":"first","affiliation":[{"name":"Huazhong University of Science and Technology , , Hongshan, ,","place":["Wuhan, P.R. 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FIRC Institute of Molecular Oncology , ,","place":["Milan, Italy, 20139"]},{"name":"Fondazione Centro Europeo Nanomedicina (CEN) , ,","place":["Milan, Italy, 20133"]},{"name":"Fondazione IRCCS Istituto Neurologico \u201cCarlo Besta\u201d , ,","place":["Milan, Italy, 20133"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Liu","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research , ,","place":["Mainz, Germany, 55128"]},{"name":"Ulm University , , ,","place":["Ulm, Germany, 89081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabyasachi","family":"Chakrabortty","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research , ,","place":["Mainz, Germany, 55128"]},{"name":"Ulm University , , ,","place":["Ulm, Germany, 89081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Krol","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico \u201cCarlo Besta\u201d , ,","place":["Milan, Italy, 20133"]},{"name":"IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d , ,","place":["Bari, Italy, 70124"]},{"name":"IRCCS Ospedale Specializzato in Gastroenterologia \u201cSaverio de Bellis\u201d , Castellana Grotte, ,","place":["Bari, Italy, 70013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Simon","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research , ,","place":["Mainz, Germany, 55128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9591-4638","authenticated-orcid":true,"given":"Katharina","family":"Landfester","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research , ,","place":["Mainz, Germany, 55128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3945-4491","authenticated-orcid":true,"given":"Seah Ling","family":"Kuan","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research , ,","place":["Mainz, Germany, 55128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-6080","authenticated-orcid":true,"given":"Francesco","family":"Stellacci","sequence":"additional","affiliation":[{"name":"Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne (EPFL) , , ,","place":["Lausanne, Switzerland, 1015"]},{"name":"Ecole Polytechnique Fe\u0301de\u0301rale de Lausanne (EPFL) , , ,","place":["Lausanne, Switzerland, 1015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-8786","authenticated-orcid":true,"given":"Klaus","family":"Mu\u0308llen","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research , ,","place":["Mainz, Germany, 55128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kreppel","sequence":"additional","affiliation":[{"name":"Ulm University , , ,","place":["Ulm, Germany, 89081"]},{"name":"Universita\u0308t Witten\/Herdecke (UW\/H) , , ,","place":["Witten, Germany, 58453"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-7205","authenticated-orcid":true,"given":"Tanja","family":"Weil","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research , ,","place":["Mainz, Germany, 55128"]},{"name":"Ulm University , , ,","place":["Ulm, Germany, 89081"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"2026090222271226800_cit1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nnano.2017.61","article-title":"Nanomedicine:\nEvolution of the Nanoparticle Corona","volume":"12","author":"Hadjidemetriou","year":"2017","journal-title":"Nat. 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Healthcare Mater."},{"key":"2026090222271226800_cit19","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1002\/marc.201300671","article-title":"Tuning Polarity of\nPolyphenylene Dendrimers by Patched Surface Amphiphilicity--Precise\nControl over Size, Shape, and Polarity","volume":"35","author":"Stangenberg","year":"2014","journal-title":"Macromol.\nRapid Commun."},{"key":"2026090222271226800_cit20","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1002\/cbic.201700079","article-title":"Controlling Cellular Uptake and Toxicity of Polyphenylene\nDendrimers by Chemical Functionalization","volume":"18","author":"Hammer","year":"2017","journal-title":"ChemBioChem"},{"key":"2026090222271226800_cit21","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1039\/a907339f","article-title":"Polyphenylene Dendrimers via Diels-Alder\nReactions: The Convergent Approach","author":"Wiesler","year":"1999","journal-title":"Chem. 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