title: A hybrid vector for ligand-directed tumor targeting and molecular imaging.
abstract: Merging tumor targeting and molecular-genetic imaging into an integrated platform is limited by lack of strategies to enable systemic yet ligand-directed delivery and imaging of specific transgenes. Many eukaryotic viruses serve for transgene delivery but require elimination of native tropism for mammalian cells; in contrast, prokaryotic viruses can be adapted to bind to mammalian receptors but are otherwise poor vehicles. Here we introduce a system containing cis-elements from adeno-associated virus (AAV) and single-stranded bacteriophage. Our AAV/phage (AAVP) prototype targets an integrin. We show that AAVP provides superior tumor transduction over phage and that incorporation of inverted terminal repeats is associated with improved fate of the delivered transgene. Moreover, we show that the temporal dynamics and spatial heterogeneity of gene expression mediated by targeted AAVP can be monitored by positron emission tomography. This new class of targeted hybrid viral particles will enable a wide range of applications in biology and medicine.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Hajitou
authors.forename: Martin
authors.initials: M
authors.lastname: Trepel
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Lilley
authors.forename: Suren
authors.initials: S
authors.lastname: Soghomonyan
authors.forename: Mian M
authors.initials: MM
authors.lastname: Alauddin
authors.forename: Frank C
authors.initials: FC
authors.lastname: Marini
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Restel
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ozawa
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Moya
authors.forename: Roberto
authors.initials: R
authors.lastname: Rangel
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Karim
authors.initials: K
authors.lastname: Zaoui
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Weitzman
authors.forename: Juri G
authors.initials: JG
authors.lastname: Gelovani
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D003952:Diagnostic Imaging; D015774:Ganciclovir / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D039564:Integrin alphaV / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D008967:Molecular Biology / Q000379:methods; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes
chemical_list: D000998:Antiviral Agents; D039564:Integrin alphaV; D008024:Ligands; D015774:Ganciclovir