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

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

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236 Scopus citations

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.

Original language	English (US)
Pages (from-to)	385-398
Number of pages	14
Journal	Cell
Volume	125
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2006.02.042
State	Published - Apr 21 2006

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Hajitou, A., Trepel, M., Lilley, C. E., Soghomonyan, S., Alauddin, M. M., Marini, F. C., Restel, B. H., Ozawa, M. G., Moya, C. A., Rangel, R., Sun, Y., Zaoui, K., Schmidt, M., von Kalle, C., Weitzman, M. D., Gelovani, J. G., Pasqualini, R., & Arap, W. (2006). A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging. Cell, 125(2), 385-398. https://doi.org/10.1016/j.cell.2006.02.042

Hajitou, A, Trepel, M, Lilley, CE, Soghomonyan, S, Alauddin, MM, Marini, FC, Restel, BH, Ozawa, MG, Moya, CA, Rangel, R, Sun, Y, Zaoui, K, Schmidt, M, von Kalle, C, Weitzman, MD, Gelovani, JG, Pasqualini, R & Arap, W 2006, 'A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging', Cell, vol. 125, no. 2, pp. 385-398. https://doi.org/10.1016/j.cell.2006.02.042

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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.",

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

note = "Funding Information: We thank Michael Andreeff, Marco Arap, Carlotta Cavazos, Toni Cathomen, Erkki Koivunen, Johanna Lahdenranta, Darwin Lee, Steven Libutti, Jude Samulski, Karen Schmidt, Richard Sidman, and Claudia Zompetta for advice, technical assistance, and reagents. Funded by grants from the NIH (including the SPORE) and DOD (including the IMPACT) and by awards from the Gillson-Longenbaugh Foundation, the Keck Foundation, and the Prostate Cancer Foundation (to R.P. and W.A.). C.E.L. received support from a Wellcome Trust International Research Fellowship. A.H. received a L{\'e}on Fredericq Award. ",

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month = apr,

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doi = "10.1016/j.cell.2006.02.042",

language = "English (US)",

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AU - Hajitou, Amin

AU - Trepel, Martin

AU - Lilley, Caroline E.

AU - Soghomonyan, Suren

AU - Alauddin, Mian M.

AU - Marini, Frank C.

AU - Restel, Bradley H.

AU - Ozawa, Michael G.

AU - Moya, Catherine A.

AU - Rangel, Roberto

AU - Sun, Yan

AU - Zaoui, Karim

AU - Schmidt, Manfred

AU - von Kalle, Christof

AU - Weitzman, Matthew D.

AU - Gelovani, Juri G.

AU - Pasqualini, Renata

AU - Arap, Wadih

N1 - Funding Information: We thank Michael Andreeff, Marco Arap, Carlotta Cavazos, Toni Cathomen, Erkki Koivunen, Johanna Lahdenranta, Darwin Lee, Steven Libutti, Jude Samulski, Karen Schmidt, Richard Sidman, and Claudia Zompetta for advice, technical assistance, and reagents. Funded by grants from the NIH (including the SPORE) and DOD (including the IMPACT) and by awards from the Gillson-Longenbaugh Foundation, the Keck Foundation, and the Prostate Cancer Foundation (to R.P. and W.A.). C.E.L. received support from a Wellcome Trust International Research Fellowship. A.H. received a Léon Fredericq Award.

PY - 2006/4/21

Y1 - 2006/4/21

N2 - 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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A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging

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