In vivo bioluminescence tumor imaging of RGD peptide-modified adenoviral vector encoding firefly luciferase reporter gene.
OBJECTIVE
The goal of this study is to demonstrate the feasibility of chemically modified human adenovirus (Ad) vectors for tumor retargeting.


METHODS
E1- and E3-deleted Ad vectors carrying firefly luciferase reporter gene under cytomegalovirus promoter (AdLuc) was surface-modified with cyclic arginine-glycine-aspartic acid (RGD) peptides through a bifunctional poly(ethyleneglycol) linker (RGD-PEG-AdLuc) for integrin alpha(v)beta(3) specific delivery. The Coxsackie and adenovirus viral receptor (CAR) and integrin alpha(v)beta(3) expression in various tumor cell lines was determined by reverse transcriptase PCR and fluorescence-activated cell sorting. Bioluminescence imaging was performed in vitro and in vivo to evaluate RGD-modified AdLuc infectivity.


RESULTS
RGD-PEG-AdLuc abrogated the native CAR tropism and exhibited significantly enhanced transduction efficiency of integrin-positive tumors than AdLuc through intravenous administration.


CONCLUSIONS
This approach provides a robust platform for site-specific gene delivery and noninvasive monitoring of the transgene delivery efficacy and homing.
Niu
Gang
G
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Xiong
Zhengming
Z
Cheng
Zhen
Z
Cai
Weibo
W
Gambhir
Sanjiv S
SS
Xing
Lei
L
Chen
Xiaoyuan
X
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics; D049409:Luciferases, Firefly / Q000235:genetics*; D008163:Luminescent Measurements; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000235:genetics; D011092:Polyethylene Glycols; D011991:Receptors, Virus / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D014161:Transduction, Genetic
C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D017931:DNA Primers; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011991:Receptors, Virus; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D049409:Luciferases, Firefly