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Titolo:
Trans-splicing ribozymes for targeted gene delivery
Autore:
Kohler, U; Ayre, BG; 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:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 5, volume: 285, anno: 1999,
pagine: 1935 - 1950
SICI:
0022-2836(19990205)285:5<1935:TRFTGD>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROUP-I INTRON; TETRAHYMENA RIBOZYME; MAMMALIAN-CELLS; ESCHERICHIA-COLI; SITE SPECIFICITY; RNA STRUCTURE; BINDING-SITE; SEQUENCE; EXPRESSION; DETERMINES;
Keywords:
Tetrahymena thermophila; gene therapy; HIV; CMV; bioassay;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Kohler, U Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England Univ Cambridge Downing St Cambridge England CB2 3EA EA, England
Citazione:
U. Kohler et al., "Trans-splicing ribozymes for targeted gene delivery", J MOL BIOL, 285(5), 1999, pp. 1935-1950

Abstract

Ribozymes are potential tools for genetic manipulation, and various naturally occurring catalytic RNAs have been dissected and used as the basis for the design of new endoribonuclease activities. While such cleaving ribozymes may work well in vitro, they have not proved to be routinely effective indepleting living cells of the chosen target RNA. Recently, trans-splicing ribozymes have been employed to repair mutant mRNAs in vivo. We have designed modified trans-splicing ribozymes with improved biological activity. These allow accurate splicing of a new 3' exon sequence into a chosen site within a target RNA, and in frame fusion of the exon can result in expression of a new gene product. These trans-splicing ribozymes contain catalytic sequences derived from a self-splicing group I intron, which have been adaptedto a chosen target mRNA by fusion of a region of extended complementarity to the target RNA and precise alteration of the guide sequences required for substrate recognition. Both modifications are required for improved biological activity of the ribozymes. Whereas cleaving ribozymes must efficiently deplete a chosen mRNA species to be effective in vivo, even inefficient trans-splicing can allow the useful expression of a new gene activity, dependent on the presence of a chosen RNA. We have targeted trans-splicing ribozymes against mRNAs of chloramphenicol acetyltransferase, human immunodeficiency virus, and cucumber mosaic virus, and demonstrated trans-splicing and delivery of a marker gene in Escherichia coli cells. The improved trans-splicing ribozymes may be tailored for virtually any target RNA, and provide anew tool for triggering gene expression in specific cell types. (C) 1999 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:55:44