Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Design of highly specific cytotoxins by using trans-splicing ribozymes
Autore:
Ayre, BG; Kohler, U; Goodman, HM; Haseloff, J;
Indirizzi:
MRC, Mol Biol Lab, Cambridge CB2 2QH, England MRC Cambridge England CB2 2QH , Mol Biol Lab, Cambridge CB2 2QH, England Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA Harvard Univ Boston MA USA 02114 ch Med, Dept Genet, Boston, MA 02114 USA Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 Mol Biol, Boston, MA 02114 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 7, volume: 96, anno: 1999,
pagine: 3507 - 3512
SICI:
0027-8424(19990330)96:7<3507:DOHSCB>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROUP-I INTRON; ACTIVE-SITE MUTATIONS; DIPHTHERIA-TOXIN; MAMMALIAN-CELLS; MEDIATED REPAIR; RNA; SEQUENCE; MESSENGER; EXPRESSION; YEAST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Haseloff, J MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England MRC Hills Rd Cambridge England CB2 2QH ridge CB2 2QH, England
Citazione:
B.G. Ayre et al., "Design of highly specific cytotoxins by using trans-splicing ribozymes", P NAS US, 96(7), 1999, pp. 3507-3512

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 invivo. Trans-splicing ribozymes may provide a new class of agents for engineering virus resistanceand therapeutic cytotoxins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 08:02:59