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Directed Evolution of Soluble IL-17A Receptor for Psoriasis Therapeutics (PSORIASIS-TREAT)
Start date: Jan 1, 2014, End date: Jun 30, 2015 PROJECT  FINISHED 

Protein therapeutics has increased dramatically over the last two decades and currently includes more than 130 therapeutic proteins in almost all fields of medicine. However, many proteins are not suitable for therapeutic application due to the lack of sufficient in vivo stability and biological efficacy. Thus, engineering of existing proteins for improved affinity and stability will significantly increase their potential for therapeutic applications. In recent years, the cytokine interleukin 17A (IL-17A) was identified as an important pro-inflammatory protein that plays an essential role in the progression of several autoimmune diseases including psoriasis, rheumatoid arthritis and inflammatory bowel disease. Thus, IL-17A is a promising drug target, and blocking its interactions with the endogenous IL-17RA receptor may constitute an important strategy for the treatment of common autoimmune diseases. We have recently applied protein engineering to generate decoy IL-17RA mutants with improved binding affinity and stability relative to the native soluble receptor. These variants showed promising results in inhibiting psoriasis plaque formation in a human psoriasis mouse model. Here, I propose to further develop the engineered IL-17RA for future pre-clinical and clinical development and pave the way for its commercialization. I propose to perform final lead optimization of the engineered IL-17RA variants by reducing the number of mutations while maintaining the improved characteristics of the engineered receptor. In parallel, I intend to perform detailed intellectual property (IP) and market analysis for identifying the ideal partner to promote the commercialization of the engineered IL-17RA. Further development of engineered IL-17RA and its commercialization will increase our chances for obtaining a highly efficient and a more affordable therapeutic approach for psoriasis and potentially for other common autoimmune diseases.
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