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Alternative Splicing as a Therapeutic Target for Human Diseases

  • Kenneth J. Dery
  • Veronica Gusti
  • Shikha Gaur
  • John E. Shively
  • Yun Yen
  • Rajesh K. Gaur
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 555)

Abstract

The majority of eukaryotic genes undergo alternative splicing, an evolutionarily conserved phenomenon, to generate functionally diverse protein isoforms from a single transcript. The fact that defective pre-mRNA splicing can generate non-functional and often toxic proteins with catastrophic effects, accurate removal of introns and joining of exons is vital for cell homeostasis. Thus, molecular tools that could either silence a disease-causing gene or regulate its expression in trans will find many therapeutic applications. Here we present two RNA-based approaches, namely RNAi and theophylline-responsive riboswitch that can regulate gene expression by loss-of-function and modulation of splicing, respectively. These strategies are likely to continue to play an integral role in studying gene function and drug discovery.

Key words

Alternative splicing spliceosome RNAi theophylline-responsive riboswitch 

Notes

Acknowledgments

We thank members of the Gaur laboratory for helpful discussions; Marieta Gencheva for valuable suggestions; and Faith Osep for administrative assistance. This work was supported in part by a Department of Defense (DOD; CDMRP) grant to RKG (BC023235), Beckman Research Institute excellence award to RKG, and NIH grant (CA 84202) to JES.

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Kenneth J. Dery
    • 1
  • Veronica Gusti
    • 2
  • Shikha Gaur
    • 3
  • John E. Shively
    • 4
  • Yun Yen
    • 5
  • Rajesh K. Gaur
    • 6
  1. 1.Divisions of Molecular Biology and ImmunologyBeckman Research Institute of the City of HopeDuarteUSA
  2. 2.Division of Molecular BiologyBeckman Research Institute of the City of HopeDuarteUSA
  3. 3.Department of Clinical and Molecular PharmacologyBeckman Research Institute of the City of HopeDuarteUSA
  4. 4.Division of ImmunologyBeckman Research Institute of the City of HopeDuarteUSA
  5. 5.Department of Clinical and Molecular PharmacologyBeckman Research Institute of the City of HopeDuarteUSA
  6. 6.Division of Molecular Biology and Graduate School of Biological SciencesBeckman Research Institute of the City of HopeDuarteUSA

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