Potent Dominant Negative Transcriptional Inhibitors

University of California System: University of California, San Francisco
posted on 11/11/2008

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BACKGROUND: The regulation of gene expression by transcription factors is a fundamental aspect of the physiology of all cells. The aberrant expression of transcription factors can lead to abnormal development and various diseases, like cancer and heart defects. One disease which might be approached by modulating transcription factor function is acquired immune deficiency syndrome (AIDS), caused by the retrovirus HIV, which incorporates itself into the host cell via reverse transcription of its RNA. Several therapeutics exist currently that target various critical points in the HIV life cycle, however, used alone, these drugs have low effectiveness and cannot prevent the virus from developing resistance to these known agents. Effective new methods of targeting underexploited aspects of the HIV life cycle, such as transcription of the HIV virus, remain desirable.

TECHNOLOGY: The present invention was conceived as a dominant negative regulator of the Tat transcription factor, thus leading to the inhibition of HIV-1 transcription. More broadly, this application can be used to generate multiple potent dominant negative regulators of transcription by linking a transcription factor to a protein that localizes to the transcriptional machinery.
For more information see: D’Orso et al., 2008. Journal of Virology, 82:9492-9504