Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution
| العنوان: | Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution |
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| المؤلفون: | Maria Pelliccia, Brenton A. G. Hammer, Tanja Weil, Patrizia Andreozzi, Weina Liu, Johanna Simon, Sabyasachi Chakrabortty, Klaus Müllen, Seah Ling Kuan, Jessica Wagner, Francesco Stellacci, Silke Krol, Katharina Landfester, Yuzhou Wu, Florian Kreppel, Marco D'Alicarnasso, Longjie Li, Larissa Frank |
| المصدر: | ACS Nano |
| بيانات النشر: | American Chemical Society, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | dendrimer corona, receptor, viruses, General Physics and Astronomy, polyphenylene dendrimers, Protein Corona, 02 engineering and technology, Gene delivery, 010402 general chemistry, 01 natural sciences, amphiphilic surface patches, coxsackie, Article, Cell membrane, Transduction (genetics), protein corona, polyphenylene dendrimer, In vivo, Dendrimer, Amphiphile, expression, medicine, General Materials Science, gene delivery, dendrimer−virus complexes, Chemistry, General Engineering, adenovirus, dendrimer-virus complexes, 021001 nanoscience & nanotechnology, gene therapy, 0104 chemical sciences, medicine.anatomical_structure, adsorption, Biophysics, 0210 nano-technology, vector, Macromolecule, surface-structure |
| الوصف: | 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,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads 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 Ads 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. Ads 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1936-086X 1936-0851 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::caa20e93c6cf2b5bc8a6100c684e1c17Test http://europepmc.org/articles/PMC6716120Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....caa20e93c6cf2b5bc8a6100c684e1c17 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1936086X 19360851 |
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