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journal article·2019-08-27Open access

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

Yuzhou Wu, Longjie Li, Larissa Frank, Jessica Wagner, Patrizia Andreozzi, Brenton Hammer, Marco D’Alicarnasso, Maria Pelliccia, Weina Liu, Sabyasachi Chakrabortty, Silke Krol, Johanna Simon, Katharina Landfester, Seah Ling Kuan, Francesco Stellacci, Klaus Müllen, Florian Kreppel, Tanja Weil

ACS Nano· Volume 13· Issue 8
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Source abstract

Abstract

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. 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-host 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.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

PolymersBiomaterials

OpenAlex topics: Virus-based gene therapy research · RNA Interference and Gene Delivery · Viral Infectious Diseases and Gene Expression in Insects

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 430074 Hongshan, Wuhan, P.R. China

Max Planck Institute for Polymer Research, 55128 Mainz, Germany

Department of Gene Therapy, Ulm University, 89081 Ulm, Germany

Graduate School Materials Science in Mainz, 55128 Mainz, Germany

IFOM - FIRC Institute of Molecular Oncology, 20139 Milan, Italy

Soft Matter Nanotechnology Group San Sebastian-Donostia, CIC biomaGUNE, 20014 Donastia San Sebastián, Spain

Fondazione Centro Europeo Nanomedicina (CEN), 20133 Milan, Italy

Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, Italy

Institute for Inorganic Chemistry I, Ulm University, 89081 Ulm, Germany

IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy

IRCCS Ospedale Specializzato in Gastroenterologia “Saverio de Bellis”, 70013 Castellana Grotte, Bari, Italy

Institute of Materials, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland

Interfaculty Bioengineering Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland

Lehrstuhl für Biochemie und Molekulare Medizin, Center for Biomedical Research and Education (ZBAF), Fakultät für Gesundheit/Department für Humanmedizin,, Universität Witten/Herdecke (UW/H), 58453 Witten, Germany

Funding

Ministry of Education of the People's Republic of China · Deutsche Forschungsgemeinschaft · National Natural Science Foundation of China · FP7 Ideas: European Research Council · Volkswagen Foundation · Central Committee of the Communist Party of China

References (33)

Show source-provided references
1. 10.1038/nnano.2017.6110.1038/nnano.2017.61 ↗
2. 10.1038/nnano.2016.26910.1038/nnano.2016.269 ↗
3. 10.1038/nnano.2012.23710.1038/nnano.2012.237 ↗
4. 10.1038/nnano.2013.18110.1038/nnano.2013.181 ↗
5. 10.1038/nnano.2015.33010.1038/nnano.2015.330 ↗
6. 10.1016/j.cbpa.2005.10.00610.1016/j.cbpa.2005.10.006 ↗
7. 10.1038/ncomms1024110.1038/ncomms10241 ↗
8. 10.1038/nmat220210.1038/nmat2202 ↗
9. 10.1038/nm.310710.1038/nm.3107 ↗
10. 10.1016/j.cell.2008.01.01610.1016/j.cell.2008.01.016 ↗
11. 10.1128/JVI.00663-0710.1128/JVI.00663-07 ↗
12. 10.1089/hum.2013.252710.1089/hum.2013.2527 ↗
13. 10.2174/15665230778085906210.2174/156652307780859062 ↗
14. 10.1128/JVI.79.12.7478-7491.200510.1128/JVI.79.12.7478-7491.2005 ↗
15. 10.1182/blood-2009-03-20883510.1182/blood-2009-03-208835 ↗
16. 10.1089/hum.2004.15.103410.1089/hum.2004.15.1034 ↗
17. 10.1002/ijc.1089110.1002/ijc.10891 ↗
18. 10.1002/adhm.20140029110.1002/adhm.201400291 ↗
19. 10.1002/marc.20130067110.1002/marc.201300671 ↗
20. 10.1002/cbic.20170007910.1002/cbic.201700079 ↗
21. 10.1039/a907339f10.1039/a907339f ↗
22. 10.1126/science.275.5304.132010.1126/science.275.5304.1320 ↗
23. 10.1016/j.bbamem.2009.11.00710.1016/j.bbamem.2009.11.007 ↗
24. 10.1039/C7NR02977B10.1039/C7NR02977B ↗
25. 10.1016/j.jaci.2017.08.04910.1016/j.jaci.2017.08.049 ↗
26. 10.1021/am404171h10.1021/am404171h ↗
27. 10.1128/JVI.01584-0710.1128/JVI.01584-07 ↗
28. 10.1038/ng0892-37210.1038/ng0892-372 ↗
29. 10.1006/mthe.2001.033010.1006/mthe.2001.0330 ↗
30. 10.1006/mthe.2000.022710.1006/mthe.2000.0227 ↗
31. 10.1182/blood-2009-12-26002610.1182/blood-2009-12-260026 ↗
32. 10.1182/blood-2006-04-00853210.1182/blood-2006-04-008532 ↗
33. 10.1038/mt.2008.13210.1038/mt.2008.132 ↗