Design and Characterization of a Twin Ribozyme for Potential Repair of a Deletion Mutation within the Oncogenic CTNNB1‐ΔS45 mRNA

• DOI: 10.1002/cmdc.201402166
• Publication Date: 2014-08-11T20:15:22Z
• Authors: Darko Balke; Irene Zieten; Anne Strahl; Oliver Müller; Sabine Müller
• Keywords: Mammalian CPEB3 ribozyme; Ligase ribozyme; VS ribozyme; Hairpin ribozyme

Abstract RNA repair is an emerging strategy for gene therapy. Conventional therapy typically relies on the addition of corrected DNA sequence a defective to restore function. As additional option, allows alteration endogenous messenger RNAs (mRNAs). mRNA either facilitated by intracellular spliceosome machinery or intrinsic catalytic activity trans ‐acting ribozymes. Previously we developed twin ribozymes, derived from hairpin ribozyme, tandem duplication and demonstrated their potential patchwise repair. Herein describe development such ribozyme deletion mutation in oncogenic CTNNB1‐ ΔS45 mRNA. We demonstrate that units within can be adapted efficiently cleave/ligate non‐consensus substrates introduction compensatory mutations ribozyme. Thus, show mediated truncated CTNNB1 transcripts (up 1000 nt length). Repair entire ‐ΔS45 mRNA, although apparently possible general, hampered vitro secondary structure transcript.