title: IIIa deleted adenovirus as a single-cycle genome replicating vector.
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.
authors.affiliation: Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Crosby
authors.affiliation: Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA; Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA; Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902, USA; Department of Immunology, Mayo Clinic, Rochester, MN 55902, USA; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA. Electronic address: mab@mayo.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D002460:Cell Line; D005260:Female; D017353:Gene Deletion; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins
keywords: Adenovirus; Amplification; Gene therapy; Replication-competent; Replication-defective; Single-cycle; Vaccines