Antitumor effects of systemically delivered adenovirus harboring trans-splicing ribozyme in intrahepatic colon cancer mouse model.

Antitumor effects of systemically delivered adenovirus harboring trans-splicing ribozyme in intrahepatic colon cancer mouse model. Research Abstract Details 

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Antitumor effects of systemically delivered adenovirus harboring trans-splicing ribozyme in intrahepatic colon cancer mouse model. Abstract Text:

Jin-Sook Jeong,Seong-Wook Lee,Seung-Hee Hong,Yoon-Jong Lee,Haeng-Im Jung,Kyung-Sook Cho,Hye-Hyun Seo,Sang-Jin Lee,Sohee Park,Min-Sun Song,Chang-Min Kim,In-Hoo Kim,Jin-Sook Jeong,Seong-Wook Lee,Seung-Hee Hong,Yoon-Jong Lee,Haeng-Im Jung,Kyung-Sook Cho,Hye-Hyun Seo,Sang-Jin Lee,Sohee Park,Min-Sun Song,Chang-Min Kim,In-Hoo Kim,Jin-Sook Jeong,Seong-Wook Lee,Seung-Hee Hong,Yoon-Jong Lee,Haeng-Im Jung,Kyung-Sook Cho,Hye-Hyun Seo,Sang-Jin Lee,Sohee Park,Min-Sun Song,Chang-Min Kim,In-Hoo Kim,

PURPOSE: Our previous studies suggested that human telomerase reverse transcriptase (hTERT) RNA-targeting trans-splicing ribozyme could be a useful tool for cancer gene therapy. Here, we investigated whether adenoviruses harboring this ribozyme can be systemically delivered to mice, and whether they selectively mark tumors expressing hTERT and sensitize them to ganciclovir treatments. EXPERIMENTAL DESIGN: We constructed adenoviral vectors containing modified hTERT-targeting trans-splicing ribozyme with downstream reporter gene (Ad-Ribo-LacZ) or suicide gene (Ad-Ribo-HSVtk) driven by a cytomegalovirus promoter. The tumor-specific trans-splicing reaction and the tumor-killing effect of adenoviruses harboring ribozyme were investigated both in vitro and in vivo using mice with intrahepatic colon cancer metastasis via systemic administration. The safety of systemic administration of the viruses was also evaluated. RESULTS: We showed that Ad-Ribo-LacZ, when injected i.v., performs a highly specific trans-splicing reaction on hTERT mRNA and that it selectively marks tumors expressing hTERT in mice. More importantly, i.v. injection of Ad-Ribo-HSVtk plus ganciclovir significantly reduced tumor burden, with minimal liver toxicity, in mice with metastatic liver cancer, compared with the untreated group (P = 0.0009). Moreover, animals receiving Ad-Ribo-HSVtk showed improved survival compared with controls (P < 0.0001). CONCLUSIONS: This study shows that systemically delivered adenovirus harboring trans-splicing ribozyme can recognize cancer-specific transcripts and reprogram them to combat the cancer cells. Use of trans-splicing ribozymes seems to be a potentially useful gene therapy for cancer.

Antitumor effects of systemically delivered adenovirus harboring trans-splicing ribozyme in intrahepatic colon cancer mouse model. Publishing Authors By Initials

JS Jeong,SW Lee,SH Hong,YJ Lee,HI Jung,KS Cho,HH Seo,SJ Lee,S Park,MS Song,CM Kim,IH Kim,JS Jeong,SW Lee,SH Hong,YJ Lee,HI Jung,KS Cho,HH Seo,SJ Lee,S Park,MS Song,CM Kim,IH Kim,JS Jeong,SW Lee,SH Hong,YJ Lee,HI Jung,KS Cho,HH Seo,SJ Lee,S Park,MS Song,CM Kim,IH Kim,

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Antitumor effects of systemically delivered adenovirus harboring trans-splicing ribozyme in intrahepatic colon cancer mouse model. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 14

Page Numbers: 281-90

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Jan

YEAR: 2008

Antitumor effects of systemically delivered adenovirus harboring trans-splicing ribozyme in intrahepatic colon cancer mouse model. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

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AFFILIATION: Authors' Affiliations: Department of Pathology and Medical Research Center for Cancer Molecular Therapy, Dong-A University College of Medicine, Busan, Korea.

Country: United States

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MEDLINETA: Clin Cancer Res

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