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VEGF-specific short hairpin RNA-expressing oncolytic adenovirus elicits potent inhibition of angiogenesis and tumor growth

 Ji Young Yoo  ;  Joo-Hang Kim  ;  Chae-Ok Yun  ;  Hye Jin Choi  ;  Nam Kyu Kim  ;  Eok-Cheon Kim  ;  Young-Guen Kwon 
 MOLECULAR THERAPY, Vol.15(2) : 295-302, 2007 
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RNA interference is being developed to treat cancer. Although highly target specific, its use has been limited by its short duration of expression. To overcome this shortcoming, we constructed an oncolytic adenovirus (Ad)-based short hairpin RNA (shRNA) expression system (Ad-DeltaB7-shVEGF) against vascular endothelial growth factor (VEGF), a key mediator in angiogenesis. To demonstrate the VEGF-specific nature of this Ad-based shRNA, replication-incompetent Ad expressing VEGF-specific shRNA (Ad-DeltaE1-shVEGF) was also generated. Ad-DeltaE1-shVEGF was highly effective in reducing VEGF expression, and elicited an antiangiogenic effect in vitro and in vivo. Similarly, Ad-DeltaB7-shVEGF exhibited potent antiangiogenic effects in the matrigel plug assay. Moreover, Ad-DeltaB7-shVEGF demonstrated a greater antitumor effect and enhanced survival compared to the cognate control oncolytic Ad, Ad-DeltaB7. Ad-DeltaB7-shVEGF induced significant reduction in tumor vasculature, verifying the antiangiogenic mechanism. Furthermore, both the duration and magnitude of gene silencing by Ad-DeltaB7-shVEGF was greater than Ad-DeltaE1-shVEGF. These results suggest that the combined effects of oncolytic viral therapy and cancer cell-specific expression of VEGF-targeted shRNA elicits greater antitumor effect than an oncolytic Ad alone.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Nam Kyu(김남규) ORCID logo https://orcid.org/0000-0003-0639-5632
Kim, Joo Hang(김주항)
Yoo, Ji Yeong(유지영)
Yun, Chae Ok(윤채옥)
Choi, Hye Jin(최혜진) ORCID logo https://orcid.org/0000-0001-5917-1400
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