Design of highly specific cytotoxins by using trans-splicing ribozymes. Ayre, B., G.; Köhler, U.; Goodman, H., M.; and Haseloff, J. Proceedings of the National Academy of Sciences of the United States of America, 96(7):3507-3512, The National Academy of Sciences, 1999.
Design of highly specific cytotoxins by using trans-splicing ribozymes [link]Website  abstract   bibtex   
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.
@article{
 title = {Design of highly specific cytotoxins by using trans-splicing ribozymes},
 type = {article},
 year = {1999},
 pages = {3507-3512},
 volume = {96},
 websites = {http://www.pnas.org/cgi/doi/10.1073/pnas.96.7.3507},
 publisher = {The National Academy of Sciences},
 institution = {Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, England.},
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 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.},
 bibtype = {article},
 author = {Ayre, Brian G and Köhler, Uwe and Goodman, Howard M and Haseloff, Jim},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {7}
}
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