PURPOSE: The goal of this study is to demonstrate the feasibility of chemically modified human adenovirus (Ad) vectors for tumor retargeting. PROCEDURES: 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. CONCLUSION: This approach provides a robust platform for site-specific gene delivery and noninvasive monitoring of the transgene delivery efficacy and homing.
PURPOSE: The goal of this study is to demonstrate the feasibility of chemically modified human adenovirus (Ad) vectors for tumor retargeting. PROCEDURES: 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. CONCLUSION: This approach provides a robust platform for site-specific gene delivery and noninvasive monitoring of the transgene delivery efficacy and homing.
Authors: S S Gambhir; J R Barrio; M E Phelps; M Iyer; M Namavari; N Satyamurthy; L Wu; L A Green; E Bauer; D C MacLaren; K Nguyen; A J Berk; S R Cherry; H R Herschman Journal: Proc Natl Acad Sci U S A Date: 1999-03-02 Impact factor: 11.205
Authors: J C Gutheil; T N Campbell; P R Pierce; J D Watkins; W D Huse; D J Bodkin; D A Cheresh Journal: Clin Cancer Res Date: 2000-08 Impact factor: 12.531
Authors: Kurt R Zinn; Tandra R Chaudhuri; April Adams Szafran; Darrell O'Quinn; Casey Weaver; Kari Dugger; Dale Lamar; Robert A Kesterson; Xiangdong Wang; Stuart J Frank Journal: ILAR J Date: 2008
Authors: C Zavaleta; A de la Zerda; Z Liu; S Keren; Z Cheng; M Schipper; X Chen; H Dai; S S Gambhir Journal: Nano Lett Date: 2008-08-07 Impact factor: 11.189
Authors: Xiujun Fan; Peigen Ren; Sabita Dhal; Gill Bejerano; Stuart B Goodman; Maurice L Druzin; Sanjiv S Gambhir; Nihar R Nayak Journal: PLoS One Date: 2011-01-21 Impact factor: 3.240