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The effect of surface modification of adenovirus with an arginine-grafted bioreducible polymer on transduction efficiency and immunogenicity in cancer gene therapy

 Pyung-Hwan Kim  ;  Tae-il Kim  ;  James W. Yockman  ;  Sung Wan Kim  ;  Chae-Ok Yun 
 BIOMATERIALS, Vol.31(7) : 1865-1874, 2010 
Journal Title
Issue Date
Adenoviridae/metabolism* ; Adenoviridae/ultrastructure ; Animals ; Arginine/metabolism* ; Arginine/pharmacology ; Cations ; Cell Death/drug effects ; Cell Line ; Coxsackie andAdenovirusReceptor-Like Membrane Protein ; GeneticTherapy* ; Humans ; Immune Evasion/drug effects ; Light ; Mice ; Neoplasms/immunology* ; Neoplasms/therapy* ; Polyamines/metabolism* ; Polyamines/pharmacology ; Polyethyleneimine/pharmacology ; Receptors, Virus/metabolism ; Reproducibility of Results ; Scattering, Radiation ; Serum ; SurfaceProperties/drug effects ; Transduction, Genetic/methods*
Cancer gene therapy ; Adenovirus ; Arginine-grafted bioreducible polymer ; Hybrid vector ; Electrostatic interaction
Adenoviral vectors offer many advantages for cancer gene therapy, including high transduction efficiency, but safety concerns related to severe immunogenicity and other side effects have led to careful reconsideration of their use in human clinical trials. To overcome these issues, a strategy of generating hybrid vectors that combine viral and non-viral elements as more intelligent gene carriers has been employed. Here, we coated adenovirus (Ad) with an arginine-grafted bioreducible polymer (ABP) via electrostatic interaction. We examined the effect of ABP-coated Ad complex at various ABP molecules/Ad particle ratios. Enhanced transduction efficiency was observed in cells treated with cationic ABP polymer-coated Ad complex compared to naked Ad. We also examined the coating of Ad with ABP polymers at the optimal polymer ratio using dynamic light scattering and transmission electron microscopy. In both high and low coxsackie virus and adenovirus receptor (CAR)-expressing cells, ABP-coated Ad complex produced higher levels of transgene expression than cationic polymer 25K PEI. Notably, high cytotoxicity was observed with 25K PEI-coated Ad complex treatment, but not with ABP-coated Ad complex treatment. In addition, ABP-coated Ad complex was not significantly inhibited by serum, in contrast to naked Ad. Moreover, ABP-coated Ad complex significantly reduced the innate immune response relative to naked Ad, as assessed by interleukin-6 (IL-6) cytokine release from macrophage cells. Overall, our studies demonstrate that Ad complex formed with ABP cationic polymer may improve the efficiency of Ad and be a promising tool for cancer gene therapy
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Pyung Hwan(김평환)
Yun, Chae Ok(윤채옥)
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