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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)8749-8759
Number of pages11
JournalACS Nano
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 27 2019

Keywords

  • adenovirus
  • amphiphilic surface patches
  • Dendrimer corona
  • Dendrimer-virus complexes
  • gene delivery
  • gene therapy
  • polyphenylene dendrimer

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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