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Cellular Oncology
Volume 30 (2008), Issue 5, Pages 397-409

Conditional Inactivation of HIF-1 Using Intrabodies

Arjan J. Groot,1 Eelke H. Gort,1 Elsken van der Wall,2 Paul J. van Diest,1 and Marc Vooijs1

1Department of Pathology, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands
2Department of Internal Medicine, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands

Copyright © 2008 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Hypoxia is a hallmark of solid cancers and triggers the transcription of genes responsible for cell survival. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) is a key regulator in this response and frequently activated in human cancer. HIF-1 activation is associated with tumor aggressiveness and poor clinical outcome and, therefore, may provide an attractive therapeutic target. Here we provide a novel approach for HIF-1 targeted therapy using single-domain llama antibodies directed against the HIF-1α oxygen dependent degradation domain which encompass the N-terminal transactivation domain. Conditional expression of HIF intrabodies in mammalian cells interfered with binding to pVHL and inhibited hypoxia induced activation of endogenous target genes. Inducible intrabody targeting is a highly specific strategy for temporal protein inactivation and may have applications for disease treatment.