| Autor: |
Eugene Zhukovsky, Araz Eivazi, Alice Kim, Lisa Cherry, Omid Vafa, Peter Cheung, Jost Vielmetter, Paul Michael Steed, Sandhya Kashi, Arthur J. Chirino, Jonathan Zalevsky, John R. Desjarlais, Linus Hyun, Marian Hwang, Christina Abbott, Rend S. Hubert, Esther Kim, David E. Szymkowski, Sarah X. Gao, C. O'Brien, James Kung, Hyo H. Chung, Malú G. Tansey, Donald O'keefe, Sean Yoder, Stephen K. Doberstein, David F. Carmichael, Karen Singer, Anton Filikov, T. Umesh S. Muchhal, Duc-Hanh T. Nguyen, Cheryl Chan, Sabrina P. Martinez, Bassil I. Dahiyat |
| Rok vydání: |
2003 |
| Předmět: |
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| Zdroj: |
Science (New York, N.Y.). 301(5641) |
| ISSN: |
1095-9203 |
| Popis: |
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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