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In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells.

Publication ,  Journal Article
Hong, S-H; Jeong, J-S; Lee, Y-J; Jung, H-I; Cho, K-S; Kim, C-M; Kwon, B-S; Sullenger, BA; Lee, S-W; Kim, I-H
Published in: Mol Ther
January 2008

We have developed and validated a new tumor-targeting gene therapy strategy based upon the targeting and replacement of human telomerase reverse transcriptase (hTERT) RNA, using a trans-splicing ribozyme. By constructing novel adenoviral vectors harboring the hTERT-targeting trans-splicing ribozymes with the downstream reporter gene (Ad-Ribo-LacZ) or suicide gene (Ad-Ribo-HSVtk) driven by the cytomegalovirus (CMV) promoter, we demonstrated that this viral system selectively marks tumor cells expressing hTERT or sensitizes tumor cells to prodrug treatments. We confirmed that Ad-Ribo-LacZ successfully and selectively delivered a ribozyme that performed a highly specific trans-splicing reaction into hTERT-expressing cancer cells, both in vitro and in a peritoneal carcinomatosis nude mouse model. We also determined that the hTERT-specific expression of the suicide gene in the Ad-Ribo-HSVtk, and treatment with the corresponding prodrug, reduced tumor progression with almost the same efficacy as the strong constitutive CMV promoter-driven adenovirus, both in cancer cell lines and in nude mouse HT-29 xenografts. These observations provide the basis for a novel approach to cancer gene therapy, and demonstrate that trans-splicing ribozymes can be employed as targeting anti-cancer agents which recognize cancer-specific transcripts and reprogram them, thereby combating cancerous cells.

Duke Scholars

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Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

January 2008

Volume

16

Issue

1

Start / End Page

74 / 80

Location

United States

Related Subject Headings

  • Transgenes
  • Trans-Splicing
  • Telomerase
  • RNA, Catalytic
  • Peritoneal Neoplasms
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Hong, S.-H., Jeong, J.-S., Lee, Y.-J., Jung, H.-I., Cho, K.-S., Kim, C.-M., … Kim, I.-H. (2008). In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells. Mol Ther, 16(1), 74–80. https://doi.org/10.1038/sj.mt.6300282
Hong, Seung-Hee, Jin-Sook Jeong, Yoon-Jong Lee, Haeng-Im Jung, Kyoung-Sook Cho, Chang-Min Kim, Byung-Su Kwon, Bruce A. Sullenger, Seong-Wook Lee, and In-Hoo Kim. “In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells.Mol Ther 16, no. 1 (January 2008): 74–80. https://doi.org/10.1038/sj.mt.6300282.
Hong S-H, Jeong J-S, Lee Y-J, Jung H-I, Cho K-S, Kim C-M, et al. In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells. Mol Ther. 2008 Jan;16(1):74–80.
Hong, Seung-Hee, et al. “In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells.Mol Ther, vol. 16, no. 1, Jan. 2008, pp. 74–80. Pubmed, doi:10.1038/sj.mt.6300282.
Hong S-H, Jeong J-S, Lee Y-J, Jung H-I, Cho K-S, Kim C-M, Kwon B-S, Sullenger BA, Lee S-W, Kim I-H. In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells. Mol Ther. 2008 Jan;16(1):74–80.

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

January 2008

Volume

16

Issue

1

Start / End Page

74 / 80

Location

United States

Related Subject Headings

  • Transgenes
  • Trans-Splicing
  • Telomerase
  • RNA, Catalytic
  • Peritoneal Neoplasms
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Humans