Retargeted and detargeted adenovirus for gene delivery to the muscle

Tien V. Nguyen, Stephanie S. Anguiano-Zarate, William E. Matchett, Mary E. Barry, Michael A Barry

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

We previously selected muscle binding peptides 12.51 and 12.52 from “context-specific” phage display libraries for introduction into adenovirus (Ad) vectors. In this work, these peptides were inserted into the hypervariable region (HVR) 5 loop of the Ad5 hexon protein to display 720 peptides per virions. HVR-12.51 and 12.52 increased transduction of C2C12 cells up to 20-fold when compared to unmodified Ad5. 12.51 increased in vivo muscle transduction 2 to 7-fold over unmodified Ad after intramuscular injection in mice and hamsters. 12.52 did not increase muscle transduction. Notably, insertion of 12.51 into the hexon reduced liver transduction 80-fold when compared to unmodified Ad5 after intravenous injection. Increased muscle transduction in mice translated into increased immune responses after gene-based vaccination. These data suggest there are merits to retargeting and detargeting benefits to modifying the hexons of Ads with peptide ligands.

Original languageEnglish (US)
Pages (from-to)118-123
Number of pages6
JournalVirology
Volume514
DOIs
StatePublished - Jan 15 2018

Keywords

  • Adenovirus
  • Detargeting
  • Hexon
  • Hypervariable region
  • Phage peptide libraries
  • Targeting

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Nguyen, T. V., Anguiano-Zarate, S. S., Matchett, W. E., Barry, M. E., & Barry, M. A. (2018). Retargeted and detargeted adenovirus for gene delivery to the muscle. Virology, 514, 118-123. https://doi.org/10.1016/j.virol.2017.10.005