Scientific Reports (Apr 2017)

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

  • Shahir S. Rizk,
  • Somnath Mukherjee,
  • Akiko Koide,
  • Shohei Koide,
  • Anthony A. Kossiakoff

DOI
https://doi.org/10.1038/s41598-017-00728-1
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 6

Abstract

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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.