Designed ankyrin repeat proteins (DARPins): binding proteins for research, diagnostics, and therapy

Annu Rev Pharmacol Toxicol. 2015;55:489-511. doi: 10.1146/annurev-pharmtox-010611-134654.

Abstract

Designed ankyrin repeat proteins (DARPins) can recognize targets with specificities and affinities that equal or surpass those of antibodies, but because of their robustness and extreme stability, they allow a multitude of more advanced formats and applications. This review highlights recent advances in DARPin design, illustrates their properties, and gives some examples of their use. In research, they have been established as intracellular, real-time sensors of protein conformations and as crystallization chaperones. For future therapies, DARPins have been developed by advanced, structure-based protein engineering to selectively induce apoptosis in tumors by uncoupling surface receptors from their signaling cascades. They have also been used successfully for retargeting viruses. In ongoing clinical trials, DARPins have shown good safety and efficacy in macular degeneration diseases. These developments all ultimately exploit the high stability, solubility, and aggregation resistance of these molecules, permitting a wide range of conjugates and fusions to be produced and purified.

Keywords: directed evolution; protein engineering; protein scaffold; sensors; tumor targeting; virus retargeting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / genetics
  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Ankyrin Repeat*
  • Drug Carriers*
  • Drug Design*
  • Genetic Therapy / methods*
  • Humans
  • Models, Molecular
  • Peptide Library
  • Protein Conformation
  • Protein Engineering / methods*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / therapeutic use*
  • Structure-Activity Relationship

Substances

  • Angiogenesis Inhibitors
  • Drug Carriers
  • Peptide Library
  • Recombinant Proteins