Genetic incorporation of a herpes simplex virus type 1 thymidine kinase and firefly luciferase fusion into the adenovirus protein IX for functional display on the virion

Qiana L. Matthews, Don A. Sibley, Hongju Wu, Jing Li, Mariam A. Stoff-Khalili, Reinhard Waehler, James Michael Mathis, David T. Curiel

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

An advantage of the adenoviral vector is its molecular flexibility, which allows for vector tropism modifications for the purpose of cell targeting. In addition to targeting ligands, the capacity to incorporate heterologous peptides has allowed capsid incorporation of other functionalities. We have defined the minor capsid protein IX (pIX) as a locus capable of presenting incorporated ligands on the virion surface. Thus, we sought to exploit the possibility of incorporating functional proteins at pIX. In our current study, we sought to expand the potential utility of our capsid labeling strategy by developing simultaneous imaging capacity for dedicated small animal positron emission tomography and bioluminescence imaging on a single adenoviral vector. Therefore, we constructed an adenovirus that incorporates a fusion protein of herpes simplex virus type 1 thymidine kinase and firefly luciferase (Luc) (TK-Luc) into adenovirus capsid pIX. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional TK-Luc as a component of their capsid surface. Most importantly, Ad-pIX-TK-Luc retained dual enzymatic functions in vitro and in vivo. This dual-modality approach will allow dynamic or real-time imaging analysis of adenovirus-based interventions with maximized analytic flexibility and enhanced resolution potential.

Original languageEnglish
Pages (from-to)510-519
Number of pages10
JournalMolecular Imaging
Volume5
Issue number4
DOIs
StatePublished - 1 Oct 2006

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Firefly Luciferases
Thymidine Kinase
Human Herpesvirus 1
Adenoviridae
Virion
Capsid
Luciferases
Capsid Proteins
Proteins
Ligands
Tropism
Positron-Emission Tomography
Peptides

Cite this

Matthews, Qiana L. ; Sibley, Don A. ; Wu, Hongju ; Li, Jing ; Stoff-Khalili, Mariam A. ; Waehler, Reinhard ; Mathis, James Michael ; Curiel, David T. / Genetic incorporation of a herpes simplex virus type 1 thymidine kinase and firefly luciferase fusion into the adenovirus protein IX for functional display on the virion. In: Molecular Imaging. 2006 ; Vol. 5, No. 4. pp. 510-519.
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Genetic incorporation of a herpes simplex virus type 1 thymidine kinase and firefly luciferase fusion into the adenovirus protein IX for functional display on the virion. / Matthews, Qiana L.; Sibley, Don A.; Wu, Hongju; Li, Jing; Stoff-Khalili, Mariam A.; Waehler, Reinhard; Mathis, James Michael; Curiel, David T.

In: Molecular Imaging, Vol. 5, No. 4, 01.10.2006, p. 510-519.

Research output: Contribution to journalArticle

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AU - Matthews, Qiana L.

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AU - Wu, Hongju

AU - Li, Jing

AU - Stoff-Khalili, Mariam A.

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AU - Mathis, James Michael

AU - Curiel, David T.

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