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

Rizk SS, Mukherjee S, Koide A, Koide S, Kossiakoff AA

Sci Rep 2017 Apr;7(1):556

PMID: 28373671

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.