![]() Also, the engineered Kunitz-type inhibitor DX-1000 is being developed as a PEG conjugate 53. Here we review the current state and clinical validation of these next-generation therapeutics.Īdnectin Affibody Anticalin DARPin antibody immunoglobulin. Nevertheless, PEGylation of the Adnectin CT-322 was successfully employed to improve the pharmacokinetics of this small protein scaffold to meet clinical needs 84. This includes the abovementioned pioneering examples as well as designed ankyrin repeat proteins (DARPins). However, despite strong interest from basic science, only a handful of those protein scaffolds have undergone biopharmaceutical development up to the clinical stage. Possibilities of engineered protein scaffolds have been explored in research, diagnostics and therapy in the last few years. These translational developments will be reviewed here. These scaffolds have demonstrated efficacy in preclinical animal models and, in some cases, clinical trials in therapy or imaging. In fact, engineered protein scaffolds with useful binding specificities, mostly directed against targets of biomedical relevance, constitute an area of active research today, which has yielded versatile reagents as laboratory tools. Validated scaffolds include the fibronectin domain, knottin, designed ankyrin repeat protein, anticalin, and affibody among others. Since then, this concept has expanded considerably, including many other protein templates. Early examples were the Affibody, Monobody (Adnectin), and Anticalin proteins, which were derived from fragments of streptococcal protein A, from the tenth type III domain of human fibronectin, and from natural lipocalin proteins, respectively. The concept of engineering robust protein scaffolds for novel binding functions emerged 20 years ago, one decade after the advent of recombinant antibody technology.
0 Comments
Leave a Reply. |