Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Ribozyme-Mediated Replacement of p53 RNA by Targeted Trans-Splicing

  • Published : 2002.10.01
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Abstract

In more than half of human tumors, the p53 tumor suppressor gene is mutated. Thus, restoration of wild-type p53 activity by repair of mutant RNA could be a potentially promissing approach to cancer treatment. To explore the potential use of RNA repair for cancer therapy, trans-splicing group I ribozymes were developed that could replace mutant p53 RNA with RNA sequence attached to the 3'end of ribozymes. By employing a mapping library of ribozymes, we first determined which regions of the p53 RNA are accessible to ribozymes, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. Next, trans-splicing ribozymes were generated that specifically recognized the sequences around these accessible regions. Subsequently, the ribozymes reacted with and altered the p53 transcripts by transferring a 3'exon tag sequence onto the targeted p53 RNA with high fidelity. Thus, these ribozymes could be utilized to repair mutant p53 in tumors, which would revert the neoplastic phenotype.

Keywords

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