Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody

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Abstract

We have utilized a high-diversity phage display library to engineer antibody fragments (Fabs) that can modulate the activity of the enzyme isocitrate dehydrogenase 1 (IDH1). We show that a conformation-specific Fab can reactivate an IDH1 mutant associated with brain tumors. The results show that this strategy is a first step towards developing "activator drugs" for a large number of genetic disorders where mutations have disrupted protein function.

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Rizk, S. S., Mukherjee, S., Koide, A., Koide, S., & Kossiakoff, A. A. (2017). Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-00728-1

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