Genetic medicine at the RNA level: Modifications of the genetic repertoire for therapeutic purposes by pre-mRNA trans-splicing

Robert G. Pergolizzi, Ronald Crystal

Research output: Contribution to journalReview article

16 Citations (Scopus)


Gene therapy is conventionally carried out by transferring genetic material to the target cell where the exogenous gene is expressed using the endogenous transcription and translation machinery in parallel with the target cell genome. This review focuses on a new paradigm of gene therapy, the use of trans-splicing to modify the genetic repertoire at the pre-mRNA level to treat genetic and acquired disorders. Therapeutic trans-splicing can be used to alter coding domains, to create novel fusion proteins, to direct gene products to various cellular compartments, and to overcome some of the limitations to vector-derived gene transfer technology, including gene therapy with large genes or with genes coding for toxic proteins. To demonstrate the potential of therapeutic trans-splicing, eukaryotic cis-splicing and trans-splicing are reviewed, followed by a discussion of strategies of therapeutic pre-mRNA trans-splicing directed by exogenous gene transfer.

Original languageEnglish
Pages (from-to)695-709
Number of pages15
JournalComptes Rendus - Biologies
Issue number8
Publication statusPublished - 1 Aug 2004
Externally publishedYes



  • Gene therapy
  • Trans-splicing

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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