Alternative protein scaffolds for molecular imaging and therapy

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations


Molecular targeting has tremendous potential to enhance the specificity and sensitivity of diagnostics and the safety and potency of therapeutics, as well as to induce unique and precise biological responses. Effective targeting requires specific binding of appropriate affinity, conjugation of effectors (e.g., toxins, radioisotopes, or fusion proteins) as needed, stable maintenance of activity, and effective delivery physiologically. Ideally, solutions to these challenges will be efficiently implemented for a multitude of molecular targets unique to the relevant pathophysiology. Protein scaffolds, molecular frameworks amenable to local diversity to introduce specific binding while retaining favorable biophysical characteristics, offer an intriguing general solution. While antibodies and their derivatives offer viable options, a host of alternative topologies prove superior in stability, size, production, and/or conjugation. Validated scaffolds include the fibronectin domain, knottin, designed ankyrin repeat protein, anticalin, and affibody among others. These scaffolds have demonstrated efficacy in preclinical animal models and, in some cases, clinical trials in therapy or imaging. These translational developments will be reviewed here. The future is bright for both antibodies and their alternatives. Research should be undertaken to identify the most efficacious scaffold for each individual clinical indication and application.

Original languageEnglish (US)
Title of host publicationEngineering in Translational Medicine
PublisherSpringer Verlag
Number of pages22
ISBN (Electronic)9781447143727
ISBN (Print)144714371X, 9781447143710
StatePublished - May 1 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Springer-Verlag London. All rights reserved.


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