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

Research output: Contribution to journal › Article › peer-review

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. © 2006 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	385-398
Number of pages	13
Journal	Cell
Volume	125
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2006.02.042
Publication status	Published - 21 Apr 2006

Keywords

Animals
metabolism: Antiviral Agents
genetics: Bacteriophages
genetics: Dependovirus
Diagnostic Imaging
metabolism: Ganciclovir
Gene Transfer Techniques
Genetic Vectors
metabolism: Integrin alphaV
Ligands
Mice
Mice, Nude
methods: Molecular Biology
Neoplasm Transplantation
metabolism: Neoplasms
methods: Transduction, Genetic
Transgenes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2006.02.042

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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

@article{217549def8c642d092a36962b121c6f5,

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. {\textcopyright} 2006 Elsevier Inc. All rights reserved.",

keywords = "Animals, metabolism: Antiviral Agents, genetics: Bacteriophages, genetics: Dependovirus, Diagnostic Imaging, metabolism: Ganciclovir, Gene Transfer Techniques, Genetic Vectors, metabolism: Integrin alphaV, Ligands, Mice, Mice, Nude, methods: Molecular Biology, Neoplasm Transplantation, metabolism: Neoplasms, methods: Transduction, Genetic, Transgenes",

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",

year = "2006",

month = apr,

day = "21",

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

language = "English",

volume = "125",

pages = "385--398",

journal = "Cell",

issn = "1097-4172",

publisher = "Elsevier BV",

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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

TY - JOUR

T1 - A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging

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

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. © 2006 Elsevier Inc. All rights reserved.

AB - 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. © 2006 Elsevier Inc. All rights reserved.

KW - Animals

KW - metabolism: Antiviral Agents

KW - genetics: Bacteriophages

KW - genetics: Dependovirus

KW - Diagnostic Imaging

KW - metabolism: Ganciclovir

KW - Gene Transfer Techniques

KW - Genetic Vectors

KW - metabolism: Integrin alphaV

KW - Ligands

KW - Mice

KW - Mice, Nude

KW - methods: Molecular Biology

KW - Neoplasm Transplantation

KW - metabolism: Neoplasms

KW - methods: Transduction, Genetic

KW - Transgenes

UR - https://www.scopus.com/pages/publications/33646034578

U2 - 10.1016/j.cell.2006.02.042

DO - 10.1016/j.cell.2006.02.042

M3 - Article

SN - 1097-4172

VL - 125

SP - 385

EP - 398

JO - Cell

JF - Cell

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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