Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing.

Journal Article

Ribozymes can be targeted to cleave specific RNAs, which has led to much interest in their potential as gene inhibitors. Such trans-cleaving ribozymes join a growing list of agents that stop the flow of genetic information. Here we describe a different application of ribozymes for which they may be uniquely suited. By targeted trans-splicing, a ribozyme can replace a defective portion of RNA with a functional sequence. The self-splicing intron from Tetrahymena thermophila was previously shown to mediate trans-splicing of oligonucleotides in vitro. As a model system for messenger RNA repair, this group I intron was re-engineered to regenerate the proper coding capacity of short, truncated lacZ transcripts. Trans-splicing was efficient in vitro and proceeded in Escherichia coli to generate translatable lacZ messages. Targeted trans-splicing represents a general means of altering the sequence of specified transcripts and may provide a new approach to the treatment of many genetic diseases.

Full Text

Duke Authors

Cited Authors

  • Sullenger, BA; Cech, TR

Published Date

  • October 13, 1994

Published In

Volume / Issue

  • 371 / 6498

Start / End Page

  • 619 - 622

PubMed ID

  • 7935797

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/371619a0

Language

  • eng

Conference Location

  • England