Design of highly specific cytotoxins by using trans-splicing ribozymes

Description:

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

Creator(s):
Creation Date: March 30, 1999
Partner(s):
UNT College of Arts and Sciences
Collection(s):
UNT Scholarly Works
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Total Uses: 52
Past 30 days: 4
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Creator (Author):
Ayre, Brian G.

University of North Texas; Medical Research Council Laboratory of Molecular Biology

Creator (Author):
Köhler, Uwe

Medical Research Council Laboratory of Molecular Biology

Creator (Author):
Haseloff, Jim

Medical Research Council Laboratory of Molecular Biology

Creator (Author):
Goodman, Howard M.

Harvard Medical School; Massachusetts General Hospital

Publisher Info:
Place of Publication: [Washington, DC]
Date(s):
  • Creation: March 30, 1999
Description:

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

Degree:
Department: Biological Sciences
Note:

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.

Physical Description:

6 p.

Language(s):
Subject(s):
Keyword(s): cytotoxins | trans-splicing | ribozymes
Source: Proceedings of the National Academy of Sciences (U.S.), 1999, Washington DC: National Academy of Sciences (U.S.), pp. 3507-3512
Partner:
UNT College of Arts and Sciences
Collection:
UNT Scholarly Works
Identifier:
  • ARK: ark:/67531/metadc83320
Resource Type: Article
Format: Text
Rights:
Access: Public
Citation:
Publication Title: Proceedings of the National Academy of Sciences (U.S.)
Volume: 96
Page Start: 3507
Page End: 3512
Peer Reviewed: Yes