Genetic medicine at the RNA level: modifications of the genetic repertoire for therapeutic purposes by pre-mRNA trans-splicing. Review uri icon

Overview

MeSH

  • Animals
  • CD40 Ligand
  • Cobra Neurotoxin Proteins
  • Exons
  • Forecasting
  • Gene Transfer Techniques
  • Genetic Vectors
  • Hemophilia A
  • Humans
  • Hypergammaglobulinemia
  • Immunoglobulin M
  • Mice
  • Mice, Knockout
  • Neoplasms, Experimental
  • Protein Subunits
  • RNA
  • RNA Splicing
  • Shiga Toxin
  • Spliceosomes

MeSH Major

  • 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.

publication date

  • August 2004

has subject area

  • Animals
  • CD40 Ligand
  • Cobra Neurotoxin Proteins
  • Exons
  • Forecasting
  • Gene Transfer Techniques
  • Genetic Diseases, Inborn
  • Genetic Therapy
  • Genetic Vectors
  • Hemophilia A
  • Humans
  • Hypergammaglobulinemia
  • Immunoglobulin M
  • Mice
  • Mice, Knockout
  • Neoplasms, Experimental
  • Protein Subunits
  • RNA
  • RNA Precursors
  • RNA Splicing
  • Shiga Toxin
  • Spliceosomes
  • Trans-Splicing

Research

keywords

  • Journal Article
  • Review

Identity

Language

  • eng

PubMed ID

  • 15506518

Additional Document Info

start page

  • 695

end page

  • 709

volume

  • 327

number

  • 8