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<h1>DESIGN</h1> | <h1>DESIGN</h1> | ||
<h3 class="ar-title">Description and Overall Design</h3> | <h3 class="ar-title">Description and Overall Design</h3> | ||
− | <h4>< | + | <h4><brRheumatoid arthritis (RA) is a serious chronic, inflammatory and systemic autoimmune disease. It occurs virtually in all races of the world. RA presents great pain and financial burden for patients, but for the time being, there is no radical cure for RA. Therefore, it is necessary to develop a kind of novel targeted cell therapy for RA. </h4> |
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<center><img src="https://static.igem.org/mediawiki/2017/5/56/T--CPU_CHINA--des-figure4.png"width = "700"></center> | <center><img src="https://static.igem.org/mediawiki/2017/5/56/T--CPU_CHINA--des-figure4.png"width = "700"></center> | ||
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+ | <h4><br>To solve the problems existing in the current treatment of RA, we design and build a brand new immunotherapy. FOXP3+ regulatory T cells, which can suppress and regulate immune reaction, are engineered by inserting a chimeric antigen receptor (CAR) using lentiviral vectors to recognize RA related inflammatory cells. At the same time, we insert another receptor to activate the functional stability pathway of regulatory T cells in the inflammatory environment, and thus making it possible for them to be more immunosuppressive and more stable in lesions in hope for a better anti-RA effect. These two redirections of the two different systems on the native regulatory T cell response ensure both the efficacy and efficiency of our novel immunotherapy for RA.</h4> | ||
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<h3 class="ar-title">SynNotch System</h3> | <h3 class="ar-title">SynNotch System</h3> | ||
<h4><br>SynNotch is a system that is capable of specifically activating the expression of the USP7 gene in an inflammatory environment, thereby maintaining the activity of Treg cells by stabilizing the FOXP3 proteins.</h4> | <h4><br>SynNotch is a system that is capable of specifically activating the expression of the USP7 gene in an inflammatory environment, thereby maintaining the activity of Treg cells by stabilizing the FOXP3 proteins.</h4> | ||
<div> | <div> | ||
<center><img src="https://static.igem.org/mediawiki/2017/5/53/T--CPU_CHINA--eng-figure3_7.png" width = "400"></center> | <center><img src="https://static.igem.org/mediawiki/2017/5/53/T--CPU_CHINA--eng-figure3_7.png" width = "400"></center> | ||
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<h4><br>In our SynNotch system, we retain the functional sequence of the transmembrane domain and the cleavage site of the Notch 1 protein. At the N-terminus, we fuse the extracellular domain of IL17RA with Notch 1 to specifically recognize IL-17A secreted by Th17 cells, so that our regulatory T cells to obtain the ability to response to IL-17A. We also connect the gene of Gal4-vp64 (a fusion protein) in the downstream of Notch 1. In the presence of inflammatory cytokines IL17A, SynNotch protein is cleaved, and thus Gal4-VP64 fusion protein is detached from the cell membrane. </h4> | <h4><br>In our SynNotch system, we retain the functional sequence of the transmembrane domain and the cleavage site of the Notch 1 protein. At the N-terminus, we fuse the extracellular domain of IL17RA with Notch 1 to specifically recognize IL-17A secreted by Th17 cells, so that our regulatory T cells to obtain the ability to response to IL-17A. We also connect the gene of Gal4-vp64 (a fusion protein) in the downstream of Notch 1. In the presence of inflammatory cytokines IL17A, SynNotch protein is cleaved, and thus Gal4-VP64 fusion protein is detached from the cell membrane. </h4> | ||
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<center><img src="https://static.igem.org/mediawiki/2017/5/5a/T--CPU_CHINA--eng-figure3_9.png" width = "700"></center> | <center><img src="https://static.igem.org/mediawiki/2017/5/5a/T--CPU_CHINA--eng-figure3_9.png" width = "700"></center> | ||
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</div> | </div> | ||
<h4><br>At the N terminus, we choose variable region of CD20 monoclonal antibody as the scFv fragment, so that it can accurately identify and bind to B lymphocyte surface antigen CD20. Then, we use two 4-1-BB sequences as a co-stimulatory signal and a CD3Z sequence as a stimulatory signal that allow the signal to be delivered to the cell at a high level, thereby activating Treg cells in the presence of CD20 B lymphocytes. </h4> | <h4><br>At the N terminus, we choose variable region of CD20 monoclonal antibody as the scFv fragment, so that it can accurately identify and bind to B lymphocyte surface antigen CD20. Then, we use two 4-1-BB sequences as a co-stimulatory signal and a CD3Z sequence as a stimulatory signal that allow the signal to be delivered to the cell at a high level, thereby activating Treg cells in the presence of CD20 B lymphocytes. </h4> |
Latest revision as of 14:36, 31 October 2017