A hybrid vector for ligand-directed tumor targeting and molecular imaging
Standard
A hybrid vector for ligand-directed tumor targeting and molecular imaging. / Hajitou, Amin; Trepel, Martin; Lilley, Caroline E; Soghomonyan, Suren; Alauddin, Mian M; Marini, Frank C; Restel, Bradley H; Ozawa, Michael G; Moya, Catherine A; Rangel, Roberto; Sun, Yan V; Zaoui, Karim; Schmidt, Manfred; von Kalle, Christof; Weitzman, Matthew D; Gelovani, Juri G; Pasqualini, Renata; Arap, Wadih.
in: CELL, Jahrgang 125, Nr. 2, 21.04.2006, S. 385-98.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
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 V
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.
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.
KW - Animals
KW - Antiviral Agents
KW - Bacteriophages
KW - Dependovirus
KW - Diagnostic Imaging
KW - Ganciclovir
KW - Gene Transfer Techniques
KW - Genetic Vectors
KW - Integrin alphaV
KW - Ligands
KW - Mice
KW - Mice, Nude
KW - Molecular Biology
KW - Neoplasm Transplantation
KW - Neoplasms
KW - Transduction, Genetic
KW - Transgenes
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, Non-P.H.S.
U2 - 10.1016/j.cell.2006.02.042
DO - 10.1016/j.cell.2006.02.042
M3 - SCORING: Journal article
C2 - 16630824
VL - 125
SP - 385
EP - 398
JO - CELL
JF - CELL
SN - 0092-8674
IS - 2
ER -