Publications [#177517] of Bruce A Sullenger

Papers Published

1. SH Hong, JS Jeong, YJ Lee, HI Jung, KS Cho, CM Kim, BS Kwon, BA Sullenger, SW Lee, IH Kim, In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells., Molecular therapy : the journal of the American Society of Gene Therapy, vol. 16 no. 1 (January, 2008), pp. 74-80, ISSN 1525-0024 [doi]
   (last updated on 2010/07/15)

   Abstract:
   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.

   Keywords:
   Adenoviridae • Animals • Cell Line, Transformed • Cell Line, Tumor • Female • Gene Expression Regulation, Neoplastic • Gene Targeting* • Genetic Vectors • HT29 Cells • Humans • Male • Mice • Mice, Inbred BALB C • Mice, Nude • Peritoneal Neoplasms • RNA, Catalytic • Telomerase • Trans-Splicing • Transgenes • administration & dosage • biosynthesis • enzymology • genetics • genetics* • metabolism* • physiology • therapy