Design of highly specific cytotoxins by using trans-splicing ribozymes

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This article discusses the design of highly specific cytotoxins by using trans-splicing ribozymes.

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6 p.

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Ayre, Brian G.; Köhler, Uwe; Haseloff, Jim & Goodman, Howard M. March 30, 1999.

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  • Ayre, Brian G. University of North Texas; Medical Research Council Laboratory of Molecular Biology
  • Köhler, Uwe Medical Research Council Laboratory of Molecular Biology
  • Haseloff, Jim Medical Research Council Laboratory of Molecular Biology
  • Goodman, Howard M. Harvard Medical School; Massachusetts General Hospital

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Description

This article discusses the design of highly specific cytotoxins by using trans-splicing ribozymes.

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6 p.

Notes

Abstract: We have designed ribozymes based on a self-splicing group I intron that can trans-splice exon sequences into a chosen RNA target to create a functional chimeric mRNA and provide a highly specific trigger for gene expression. We have targeted ribozymes against the coat protein mRNA of a widespread plant pathogen, cucumber mosaic virus. The ribozymes were designed to trans-splice the coding sequence of the diphtheria toxin A chain in frame with the viral initiation codon of the target sequence. Diphtheria toxin A chain catalyzes the ADP ribosylation of elongation factor 2 and can cause the cessation of protein translation. In a Saccharomyces cerevisiae model system, ribozyme expression was shown to specifically inhibit the growth of cells expressing the virus mRNA. A point mutation at the target splice site alleviated this ribozyme-mediated toxicity. Increasing the extent of base pairing between the ribozyme and target dramatically increased specific expression of the cytotoxin and reduced illegitimate toxicity in vivo. Trans-splicing ribozymes may provide a new class of agents for engineering virus resistance and therapeutic cytotoxins.

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Source

  • Proceedings of the National Academy of Sciences (U.S.), 1999, Washington DC: National Academy of Sciences (U.S.), pp. 3507-3512

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Publication Information

  • Publication Title: Proceedings of the National Academy of Sciences (U.S.)
  • Volume: 96
  • Page Start: 3507
  • Page End: 3512
  • Peer Reviewed: Yes

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UNT Scholarly Works

The Scholarly Works Collection is home to materials from the University of North Texas community's research, creative, and scholarly activities and serves as UNT's Open Access Repository. It brings together articles, papers, artwork, music, research data, reports, presentations, and other scholarly and creative products representing the expertise in our university community. Access to some items in this collection may be restricted.

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  • March 30, 1999

Added to The UNT Digital Library

  • April 23, 2012, 10:02 a.m.

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  • March 27, 2014, 4:12 p.m.

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Ayre, Brian G.; Köhler, Uwe; Haseloff, Jim & Goodman, Howard M. Design of highly specific cytotoxins by using trans-splicing ribozymes, article, March 30, 1999; [Washington, DC]. (digital.library.unt.edu/ark:/67531/metadc83320/: accessed May 29, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.