期刊
SCIENTIFIC REPORTS
卷 1, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep00124
关键词
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资金
- Royal Society
- National Basic Research Program of China [2007CB936000]
- Science and Technology Commission of Shanghai Municipality [1052nm07700, 10PJ1405100]
- Chinese Academy of Sciences [2009YA1-1]
- MRC
- Egyptian government
- Norwegian Research Council [179573/V40]
- South-Eastern Norway Regional Health Authority [39375]
- K.C. Wong Foundation
The success of Fc-fusion bio-therapeutics has spurred the development of other Fc-fusion products for treating and/or vaccinating against a range of diseases. We describe a method to modulate their function by converting them into well-defined stable polymers. This strategy resulted in cylindrical hexameric structures revealed by tapping mode atomic force microscopy (AFM). Polymeric Fc-fusions were significantly less immunogenic than their dimeric or monomeric counterparts, a result partly owing to their reduced ability to interact with critical Fc-receptors. However, in the absence of the fusion partner, polymeric IgG1-Fc molecules were capable of binding selectively to Fc gamma Rs, with significantly increased affinity owing to their increased valency, suggesting that these reagents may prove of immediate utility in the development of well-defined replacements for intravenous immunoglobulin (IVIG) therapy. Overall, these findings establish an effective IgG Fc-fusion based polymeric platform with which the therapeutic and vaccination applications of Fc-fusion immune-complexes can now be explored.
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