Effective inhibition of C3a-mediated pro-inflammatory response by a human C3a-specific protein binder

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Complement component 3a (C3a) plays a crucial role in the immune response and host defense, but it is also involved in pro-inflammatory responses, causing many inflammatory disorders. Blockade of C3a has been regarded as a potent therapeutic strategy for inflammatory diseases. Here, we present the development of a human C3a (hC3a)-specific protein binder, which effectively inhibits pro-inflammatory responses. The protein binder, which is composed of leucine-rich repeat modules, was selected against hC3a through phage display, and its binding affinity was matured up to 600 pM by further expanding the binding interface in a module-by-module manner. The developed protein binder was shown to have more than 10-fold higher specificity to hC3a compared with human C5a, exhibiting a remarkable suppression effect on pro-inflammatory response in monocyte, by blocking the interaction between hC3a and its receptor. The hC3a-specific protein binder is likely to have a therapeutic potential for C3a-mediated inflammatory diseases.
Publisher
WILEY
Issue Date
2020-06
Language
English
Article Type
Article
Citation

BIOTECHNOLOGY AND BIOENGINEERING, v.117, no.6, pp.1904 - 1908

ISSN
0006-3592
DOI
10.1002/bit.27309
URI
http://hdl.handle.net/10203/274302
Appears in Collection
BS-Journal Papers(저널논문)
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