Publications [#99812] of Bruce A Sullenger

Papers Published

1. BA Sullenger, TR Cech, Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing., Nature, vol. 371 no. 6498 (October, 1994), pp. 619-22, ISSN 0028-0836 [doi]
   (last updated on 2013/05/16)

   Abstract:
   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.

   Keywords:
   Animals • Base Sequence • DNA, Protozoan • Escherichia coli • Introns • Lac Operon • Molecular Sequence Data • RNA Splicing* • RNA, Catalytic • RNA, Messenger • RNA, Protozoan • Tetrahymena thermophila • genetics • metabolism • metabolism*