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| <link rel="stylesheet" href="https://2018.igem.org/wiki/index.php?title=Template:SMMU-China/CSS_histogram&action=raw&ctype=text/css" /> | | <link rel="stylesheet" href="https://2018.igem.org/wiki/index.php?title=Template:SMMU-China/CSS_histogram&action=raw&ctype=text/css" /> |
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| + | <style type="text/css"> |
| + | .toggle { |
| + | display: block; |
| + | height: 72px; |
| + | line-height: 72px; |
| + | text-align: center; |
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| + | </style> |
| <div id="page-wrapper"> | | <div id="page-wrapper"> |
| <!-- Header --> | | <!-- Header --> |
| <section id="header"> | | <section id="header"> |
| | | |
− | <table> | + | <div id="needshow" style="display: none;"> |
| + | <h1><a href="https://2018.igem.org/Team:SMMU-China">Ca<sup>2+</sup>RTIN</a></h1> |
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| <th style="float:left;margin-left:40px"> | | <th style="float:left;margin-left:40px"> |
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| <tr> | | <tr> |
| </table> | | </table> |
| + | |
| + | <nav class="sidenav" data-sidenav data-sidenav-toggle="#sidenav-toggle"> |
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| + | <li><a href="https://2018.igem.org/Team:SMMU-China/Team">Team Members</a></li> |
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| + | </nav> |
| </section> | | </section> |
| | | |
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| Adeno-associated virus (AAV) is a non-enveloped virus that can be engineered to deliver DNA to target cells and has attracted a significant amount of attention in the field of gene therapy. It has various advantages such as high transduction efficiency, low probability of immune response, and long-term gene transfer potential in slowly dividing or non-dividing cells. So far, several AAV serotypes have been discovered, and each of them has diverse tissue specificity. For example, AAV serotype 9 has a high cardiomyocyte specificity, thus has emerged as a new and promising vector for gene therapy of heart diseases. In our experiment, we verified that AAV-9 vector has a high specificity and efficiency. | | Adeno-associated virus (AAV) is a non-enveloped virus that can be engineered to deliver DNA to target cells and has attracted a significant amount of attention in the field of gene therapy. It has various advantages such as high transduction efficiency, low probability of immune response, and long-term gene transfer potential in slowly dividing or non-dividing cells. So far, several AAV serotypes have been discovered, and each of them has diverse tissue specificity. For example, AAV serotype 9 has a high cardiomyocyte specificity, thus has emerged as a new and promising vector for gene therapy of heart diseases. In our experiment, we verified that AAV-9 vector has a high specificity and efficiency. |
| </p> | | </p> |
− | <div style="text-align:center" class="resultimage">
| + | |
− | <img src="https://static.igem.org/mediawiki/2018/a/a1/T--SMMU-China--Part_Collection_Pic_1.jpg" style="width: 60%;">
| + | |
− | <p style="font-style: italic;text-align: center;padding: 0em 100px 1em;">
| + | |
− | <strong>The mechanism of BNP promoter driven AR185 inhibiting RyR2 phosphorylation</strong>
| + | |
− | </p>
| + | |
− | </div>
| + | |
| <div id="to_BNP" style="height: 15px"></div> | | <div id="to_BNP" style="height: 15px"></div> |
| <h3 class="inner-h">Precision guidance: BNP promoter</h3> | | <h3 class="inner-h">Precision guidance: BNP promoter</h3> |
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| <h3 class="inner-h">Warhead: AR185</h3> | | <h3 class="inner-h">Warhead: AR185</h3> |
| <p class="inner-text"> | | <p class="inner-text"> |
− | A large number of animal experiments support that PKA catalyze the hyperphosphorylation of RyR2-S2808 in ischemic cardiomyopathy, result in calcium leakage, destroying calcium homeostasis and promoting heart failure. Based on these, we have consulted with our primary PI, Professor Shi Hu, who is a leading scientist in the field of Antibody Engineering. He introduced a novel nanobody termed AR185 which has been recently developed by his group and showed specifically inhibition of RyR2 phosphorylation In vitro. | + | AR185 is a RyR2-specific VHH antibody which is designed to inhibit RyR2 phosphorylation. It was isolated from a camelid VHH antibody library via phage display screening which is a technique received the Nobel Prize in Chemistry this year (2018). VHH, also called nanobody, derives from the variable domains of camelid heavy-chain-only antibody. Compared to the conventional antibodies, VHH has a much lower molecular weight, is a qualified candidate for intracellular antibody. |
− | </p>
| + | |
− | <p class="inner-text">
| + | |
− | A few studies have mutated the serine at the S2808 site in mouse RyR2 to alanine, so that the 2808 site cannot bind to the phosphate residue, Mutation blocked RyR2 phosphorylation at this site, and did not cause dysfunction of RyR2 meanwhile phosphorylation level of RyR2 Protein is reduced, FKBP12.6 dissociation is reduced, and calcium leakage is also obviously reduced. We believe that AR185 can also have a similar effect to the mutation of RyR2, and it can eliminate the negative effects of hyperphosphorylation, just like the warhead bomb out the target. Since it is difficult to establish a model of hyperphosphorylation of RyR2 in vitro, we plan to express antibodies and evaluate the effect in animals.
| + | |
| </p> | | </p> |
| | | |
| + | <div style="text-align:center" class="resultimage"> |
| + | <img src="https://static.igem.org/mediawiki/2018/a/a1/T--SMMU-China--Part_Collection_Pic_1.jpg" style="width: 40%;"> |
| + | <p style="font-style: italic;text-align: center;padding: 0em 100px 1em;"> |
| + | <strong>The mechanism of BNP promoter driven AR185 inhibiting RyR2 phosphorylation</strong> |
| + | </p> |
| + | </div> |
| | | |
| <div id="to_references" style="height: 15px"></div> | | <div id="to_references" style="height: 15px"></div> |
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