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 Garcia-Blanco

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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
Volume4
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Trans-Splicing
Spliceosomes
Messenger RNA
Inborn Genetic Diseases
Proteins
Human Genome
Human Activities
Exons

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Messenger RNA repair and restoration of protein function by spliceosome-mediated RNa trans-splicing. / Puttaraju, M.; DiPasquale, Janet; Baker, Carl C.; Mitchell, Lloyd G.; Garcia-Blanco, Mariano.

In: Molecular Therapy, Vol. 4, No. 2, 2001, p. 105-114.

Research output: Contribution to journalArticle

Puttaraju, M. ; DiPasquale, Janet ; Baker, Carl C. ; Mitchell, Lloyd G. ; Garcia-Blanco, Mariano. / Messenger RNA repair and restoration of protein function by spliceosome-mediated RNa trans-splicing. In: Molecular Therapy. 2001 ; Vol. 4, No. 2. pp. 105-114.
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