Article

DARPins: A true alternative to antibodies

Molecular Partners AG, Grabenstrasse 11a, 8952 Schlieren, Switzerland.
Current opinion in drug discovery & development (Impact Factor: 5.12). 04/2007; 10(2):153-9.
Source: PubMed

ABSTRACT Designed ankyrin repeat proteins (DARPins) are a promising class of non-immunoglobulin proteins that can offer advantages over antibodies for target binding in drug discovery and drug development. DARPins have been successfully used, for example, for the inhibition of kinases, proteases and drug-exporting membrane proteins. DARPins specifically targeting the cancer marker HER2 have also been generated and were shown to function in both in vitro diagnostics and in vivo tumor targeting. DARPins are ideally suited for in vivo imaging or delivery of toxins or other therapeutic payloads because of their favorable molecular properties, including small size and high stability. The low-cost production in bacteria and the rapid generation of many target-specific DARPins make the DARPin approach useful for drug discovery. Additionally, DARPins can be easily generated in multispecific formats, offering the potential to target an effector DARPin to a specific organ or to target multiple receptors with one molecule composed of several DARPins.

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    • "that make up the energy landscape of D34 and pointing to an interesting mechanism by which the folding and, thereby, the function of tandem-repeat proteins can be regulated. This mechanism could be also be exploited to regulate the binding properties of designed ankyrin-repeat proteins, which are currently in development as alternatives to therapeutic antibodies (Stumpp and Amstutz, 2007). "
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    • "The assembled protein consists of two capping repeats intervened by two or more binding modules that are randomly modified on their surface. Combinatorial libraries with DARPins of varying repeat numbers have been constructed and have been used for selections against a wide range of targets [28] [29] [30] [31] [32] [33] [34], reviewed recently [35] [36]. In the field of allergy, we have recently characterized bispecific DARPins that 0165-2478/$ – see front matter © 2010 Elsevier B.V. All rights reserved. "
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