Publication Type	Review
Authors	Pergolizzi R, Crystal R
Journal	C R Biol
Volume	327
Issue	8
Pagination	695-709
Date Published	08/01/2004
ISSN	1631-0691
Keywords	Genetic Diseases, Inborn, Genetic Therapy, RNA Precursors, Trans-Splicing
Abstract	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.
DOI	10.1016/j.crvi.2004.05.008
PubMed ID	15506518