Messenger RNA repair and restoration of protein function by spliceosome-mediated RNa trans-splicing

M. Puttaraju, Janet DiPasquale, Carl C. Baker, Lloyd G. Mitchell, Mariano A. Garcia-Blanco

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


The functional repertoire of the human genome is amplified by the differential assortment of exons. Spliceosome-mediated RNA trans-splicing can mobilize these packets of genetic information to reprogram mRNAs. In principle, this process could repair defective transcripts in loss-of-function genetic disorders in humans. We developed a tractable lacZ repair system to serve as a model for these genetic disorders. Targeted pre-trans-splicing RNA molecules efficiently and specifically repaired mutated lacZ transcripts and restored enzymatic activity in human cells. The development of this model confirms the potential for spliceosome-mediated RNA trans-splicing in genetic repairs and provides a powerful tool for rational design and in vitro evolution of pre-trans-splicing molecules.

Original languageEnglish (US)
Pages (from-to)105-114
Number of pages10
JournalMolecular Therapy
Issue number2
StatePublished - 2001
Externally publishedYes


  • Gene therapy
  • Genetic disease
  • RNA repair
  • Trans-splicing

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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