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