A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging

Amin Hajitou; Martin Trepel; Caroline E Lilley; Suren Soghomonyan; Mian M Alauddin; Frank C Marini; Bradley H Restel; Michael G Ozawa; Catherine A Moya; Roberto Rangel; Yan Sun; Karim Zaoui; Manfred Schmidt; Christof von Kalle; Matthew D Weitzman; Juri G Gelovani; Renata Pasqualini; Wadih Arap

doi:10.1016/j.cell.2006.02.042

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A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging

Journal article

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Peer reviewed

A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging

Amin Hajitou, Martin Trepel, Caroline E Lilley, Suren Soghomonyan, Mian M Alauddin, Frank C Marini, Bradley H Restel, Michael G Ozawa, Catherine A Moya, Roberto Rangel, …

Cell, Vol.125(2), pp.385-398

2006

DOI: https://doi.org/10.1016/j.cell.2006.02.042

PMID: 16630824

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.

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Title: A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging
Creators: Amin Hajitou - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Martin Trepel - Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany
Caroline E Lilley - The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
Suren Soghomonyan - Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Mian M Alauddin - Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Frank C Marini - Department of Bone Marrow Transplantation, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Bradley H Restel - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Michael G Ozawa - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Catherine A Moya - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Roberto Rangel - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Yan Sun - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Karim Zaoui - Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany
Manfred Schmidt - Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany
Christof von Kalle - Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany
Matthew D Weitzman - The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
Juri G Gelovani - Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Renata Pasqualini - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Wadih Arap - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Publication Details: Cell, Vol.125(2), pp.385-398
Date published: 2006
Publisher: Elsevier Inc
Academic Unit: Cancer Institute of New Jersey at University Hospital; Radiation Oncology
Language: English
Resource Type: Journal article
Identifiers: 991031654031604646