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

1 Citation (Scopus)

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

Fingerprint

Adenoviridae
Muscles
Peptides
Genes
Intramuscular Injections
Intravenous Injections
Cricetinae
Virion
Bacteriophages
Libraries
Vaccination
Ligands
Liver
Proteins

Keywords

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

ASJC Scopus subject areas

  • Virology

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

Retargeted and detargeted adenovirus for gene delivery to the muscle. / Nguyen, Tien V.; Anguiano-Zarate, Stephanie S.; Matchett, William E.; Barry, Mary E.; Barry, Michael A.

In: Virology, Vol. 514, 15.01.2018, p. 118-123.

Research output: Contribution to journalArticle

Nguyen, TV, Anguiano-Zarate, SS, Matchett, WE, Barry, ME & Barry, MA 2018, 'Retargeted and detargeted adenovirus for gene delivery to the muscle', Virology, vol. 514, pp. 118-123. https://doi.org/10.1016/j.virol.2017.10.005
Nguyen, Tien V. ; Anguiano-Zarate, Stephanie S. ; Matchett, William E. ; Barry, Mary E. ; Barry, Michael A. / Retargeted and detargeted adenovirus for gene delivery to the muscle. In: Virology. 2018 ; Vol. 514. pp. 118-123.
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