IIIa deleted adenovirus as a single-cycle genome replicating vector

Catherine M. Crosby, Michael A. Barry

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Replication competent adenovirus (RC-Ad) vectors mediate robust transgene expression by virtue of amplifying transgenes by replication but also put patients at a risk of frank adenovirus infection. In contrast, E1-deleted replication defective Ad (RD-Ad) vectors are safer but produce substantially less transgene product. To generate a robust, but safer adenoviral vector, we created a "single cycle" adenovirus (SC-Ad) vector that replicates its genome and transgene, but that does not cause adenovirus infections by deleting the capsid cement protein IIIa in low seroprevalence adenovirus serotype 6. Ad6-δIIIa can be produced in IIIa-expressing cell lines. In normal cells, Ad6-δIIIa replicates its genome and transgene but fails to package its DNA or form mature virus. SC-Ad and RC-Ad expressed transgenes hundreds of times higher than RD-Ad in human and mouse cells in vitro and in vivo in mice. These data suggest that SC-Ads may be safer amplifying vectors for vaccine and therapeutic applications.

Original languageEnglish (US)
Pages (from-to)158-165
Number of pages8
JournalVirology
Volume462-463
Issue number1
DOIs
StatePublished - Aug 2014

Keywords

  • Adenovirus
  • Amplification
  • Gene therapy
  • Replication-competent
  • Replication-defective
  • Single-cycle
  • Vaccines

ASJC Scopus subject areas

  • Virology

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