A hybrid vector for ligand-directed tumor targeting and molecular imaging.
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.
Hajitou
Amin
A
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Trepel
Martin
M
Lilley
Caroline E
CE
Soghomonyan
Suren
S
Alauddin
Mian M
MM
Marini
Frank C
FC
Restel
Bradley H
BH
Ozawa
Michael G
MG
Moya
Catherine A
CA
Rangel
Roberto
R
Sun
Yan
Y
Zaoui
Karim
K
Schmidt
Manfred
M
von Kalle
Christof
C
Weitzman
Matthew D
MD
Gelovani
Juri G
JG
Pasqualini
Renata
R
Arap
Wadih
W
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
D000998:Antiviral Agents; D039564:Integrin alphaV; D008024:Ligands; D015774:Ganciclovir