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Gene therapy for Glut1Glut1 ‐deficient mouse using an adeno‐associated virus vector with the human intrinsic GLUT1 promoter

机译:使用腺相关病毒载体与人体内在的Glut1启动子使用腺相关病毒载体,基因治疗 Glut1 Glut1 -Defigle鼠标

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Abstract <section xml:id="jgm3013-sec-0001" numbered="no"> <title type="main">Background > We generated an adeno‐associated virus (AAV) vector in which the human <fi>SLC2A1</fi> gene, encoding glucose transporter type 1 (GLUT1), was expressed under the human endogenous GLUT1 promoter (AAV‐GLUT1). We examined whether AAV‐GLUT1 administration could lead to functional improvement in <fi>GLUT1</fi> ‐deficient mice. </section> <section xml:id="jgm3013-sec-0002" numbered="no"> <title type="main">Methods > We extrapolated human endogenous GLUT1 promoter sequences from rat minimal Glut1 promoter sequences. We generated a tyrosine‐mutant AAV9/3 vector in which human <fi>SLC2A1‐myc‐DDK</fi> was expressed under the human GLUT1 promoter (AAV‐GLUT1). AAV‐GLUT1 was administered to <fi>GLUT1</fi> ‐deficient mice (GLUT1 +/– mice) via intracerebroventricular injection (1.85 × 10 10 vg/mouse or 6.5 × 10 10 vg/mouse). We analyzed exogenous GLUT1 mRNA and protein expression in the brain and other major organs. We also examined improvements of cerebral microvasculature, motor function using rota‐rod and footprint tests, as well as blood and cerebrospinal fluid (CSF) glucose levels. Additionally, we confirmed exogenous GLUT1 protein distribution in the brain and other organs after intracardiac injection (7.8 × 10 11 vg/mouse). </section> <section xml:id="jgm3013-sec-0003" numbered="no"> <title type="main">Results >Exogenous GLUT1 protein was strongly expressed in the cerebral cortex, hippocampus and thalamus. It was main </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译:</span><Abstract Type =“main”XML:lang =“en”> <标题类型=“main”>抽象</ title> <section XML:ID =“JGM3013-SEC-0001”编号=“否”> <标题类型=“main”>背景</标题> >我们生成了腺相关病毒(aav)载体,其中人<fi> slc2a1 </ fi>基因编码葡萄糖转运蛋白1(glut1),在下面表达人类内源性胶水1启动子(AAV-GLUT1)。我们检查了AAV-Glut1给药是否可能导致<fi> glut1-lefite小鼠的功能改进。 </ p> </ section> <section XML:ID =“JGM3013-SEC-0002”编号=“否”> <标题类型=“main”>方法</ title> >我们外推人内源性胶质促进剂序列来自大鼠最小的Glut1启动子序列。我们产生了一种酪氨酸突变体AAV9 / 3载体,其中人<fi> slc2a1-myc-ddk </ fi>在人类露饰1启动子(aav-glut1)下表达。通过脑室注射(1.85×10 10 </ sup> Vg /小鼠或6.5×10 10 </ sup> vg /鼠标)。我们分析了大脑和其他主要器官中外源性的Glut1 mRNA和蛋白质表达。我们还检查了使用Rota-Rod和足迹测试的脑微血管系统,电机功能的改善,以及血液和脑脊液(CSF)葡萄糖水平。此外,我们确认了心房注射后脑和其他器官的外源性胶水1蛋白分布(7.8×10 11 </ sup> Vg /小鼠)。 </ p> </ section> <section XML:ID =“JGM3013-SEC-0003”编号=“否”> <标题类型=“main”>结果</标题> >外源性胶质1蛋白强烈表达脑皮质,海马和丘脑。这是主要的 </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-30882/'>《The journal of gene medicine》</a> <b style="margin: 0 2px;">|</b><span>2018年第4期</span><b style="margin: 0 2px;">|</b><span>共15页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Nakamura Sachie&option=202" target="_blank" rel="nofollow">Nakamura Sachie;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Muramatsu Shin‐ichi&option=202" target="_blank" rel="nofollow">Muramatsu Shin‐ichi;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Takino Naomi&option=202" target="_blank" rel="nofollow">Takino Naomi;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Ito Mika&option=202" target="_blank" rel="nofollow">Ito Mika;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Jimbo Eriko F.&option=202" target="_blank" rel="nofollow">Jimbo Eriko F.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shimazaki Kuniko&option=202" target="_blank" rel="nofollow">Shimazaki Kuniko;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Onaka Tatsushi&option=202" target="_blank" rel="nofollow">Onaka Tatsushi;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Ohtsuki Sumio&option=202" target="_blank" rel="nofollow">Ohtsuki Sumio;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Terasaki Tetsuya&option=202" target="_blank" rel="nofollow">Terasaki Tetsuya;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yamagata Takanori&option=202" target="_blank" rel="nofollow">Yamagata Takanori;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Osaka Hitoshi&option=202" target="_blank" rel="nofollow">Osaka Hitoshi;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of PediatricsJichi Medical UniversityTochigi Japan;</p> <p>Division of NeurologyJichi Medical UniversityTochigi Japan;</p> <p>Division of NeurologyJichi Medical UniversityTochigi Japan;</p> <p>Division of NeurologyJichi Medical UniversityTochigi Japan;</p> <p>Department of PediatricsJichi Medical UniversityTochigi Japan;</p> <p>Department of NeurosurgeryJichi Medical UniversityTochigi Japan;</p> <p>Division of Brain and Neurophysiology Department of PhysiologyJichi Medical UniversityTochigi Japan;</p> <p>Department of Pharmaceutical Microbiology Faculty of Life SciencesKumamoto UniversityKumamoto Japan;</p> <p>Division of Membrane Transport and Drug Targeting Graduate School of Pharmaceutical SciencesTohoku UniversitySendai Japan;</p> <p>Department of PediatricsJichi Medical UniversityTochigi Japan;</p> <p>Department of PediatricsJichi Medical UniversityTochigi Japan;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1473.html" title="医学遗传学">医学遗传学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=adeno‐associated virus (AAV)&option=203" rel="nofollow">adeno‐associated virus (AAV);</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=gene therapy&option=203" rel="nofollow">gene therapy;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=glucose transporter 1 deficiency syndrome (GLUT1DS)&option=203" rel="nofollow">glucose transporter 1 deficiency syndrome (GLUT1DS);</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=GLUT1&option=203" rel="nofollow">GLUT1;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=SLC2A1&option=203" rel="nofollow">SLC2A1;</a> </p> <div class="translation"> 机译:腺相关病毒(AAV);基因治疗;葡萄糖转运蛋白1缺乏综合征(Glut1ds);Glut1;SLC2A1; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity 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S.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Belldegrun, A. S. </a> <span>2002</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:前列腺特异性基因治疗使用表达反义TGF-β和psa启动子控制的TNF-α基因的'Gutless'腺病毒载体。</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-journal-pathophysiology_thesis/0201223431705.html">大鼠GLUT1基因的扩增及其重组腺病毒载体的构建</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李方成&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 李方成</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李军亮&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,李军亮</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=梁伟强&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,梁伟强</a> <span> <a href="/journal-cn-5784/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国病理生理杂志 </a> </span> <span> . 2006</span><span>,第011期</span> </span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-journal-pathophysiology_thesis/0201223453490.html">大鼠GLUT1真核表达载体的构建及其在293细胞中的表达</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李方成&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 李方成</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李军亮&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,李军亮</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=刘然义&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,刘然义</a> <span> <a href="/journal-cn-5784/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国病理生理杂志 </a> </span> <span> . 2005</span><span>,第010期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-cn_international-journal-biologicals_thesis/0201222343805.html">基因免疫使用的腺相关病毒载体</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=张丽旌&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 张丽旌</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=孙茂盛&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,孙茂盛</a> <span> <a href="/journal-cn-5757/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 国际生物制品学杂志 </a> </span> <span> . 2003</span><span>,第004期</span> </span> </div> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-journal-cn_microcomputer-information_thesis/0201280164502.html">腺相关病毒载体在基因治疗领域中的应用和挑战</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=谭靓&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 谭靓</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李泰明&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,李泰明</a> <span> <a href="/journal-cn-8933/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 微计算机信息 </a> </span> <span> . 2020</span><span>,第013期</span> </span> </div> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-journal-cn_science-technology-innovation_thesis/0201281483587.html">腺相关病毒载体在基因治疗领域中的应用和挑战</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=谭靓&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 谭靓</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李泰明&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,李泰明</a> <span> <a href="/journal-cn-21767/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 科技与创新 </a> </span> <span> . 2020</span><span>,第013期</span> </span> </div> </li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-conference-cn_meeting-40735_thesis/020222442128.html">低蛋白日粮添加异亮氨酸上调断奶仔猪肌肉葡萄糖转运载体GLUT1和GLUT4以及肠道葡萄糖转运载体SGLT-1的表达</a> <b>[C]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=ZHANG Shi-hai&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . ZHANG Shi-hai</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=张世海&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,张世海</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=YANG Qing&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,YANG Qing</a> <span> <a href="/conference-cn-40735/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 第七届中国畜牧科技论坛 </a> <span> <span> . 2016</span> </span> </div> </li> <li> <div> <b>7. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020315001326.html">以重组腺相关病毒为载体、人端粒酶逆转录酶启动子靶向调控的重组活性caspase-3基因治疗人卵巢癌的实验研究</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=何春霞&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 何春霞</a> <span> . 2006</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06120110112440.html">重组GLUT1腺相关病毒载体构建体以及用于恢复GLUT1表达的相关方法</a> <b>[P]</b> . <span> 中国专利: CN107635575A </span> <span> . 2018-01-26</span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06120100948583.html">生产高产重组腺相关病毒(rAAV)载体可扩展高回收法及其产生的重组腺相关病毒(rAAV)载体</a> <b>[P]</b> . <span> 中国专利: CN109790549A </span> <span> . 2019-05-21</span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130422892569.html">(54) Title: METHODS OF PROPAGATING MONKEY ADENOVIRAL VECTORS (57) Abstract: The invention provides methods for propagating a monkey adenovirus in a cell including a human cell, comprising one or more gene products isolated from a human adenovirus. Also" provided are methods for propagating wherein the monkey adenovirus comprises a nucleic acid sequence encoding a human adenovirus gene product. The invention further provides a monkey adenovirus, including a replication-deficient monkey adenovirus, obtained by such propagation methods.</a> <b>[P]</b> . <span> 外国专利: <!-- --> IN2012MN01301A </span> <span> . 2012-08-24</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:(54)标题:传播猴腺病毒载体的方法(57)摘要:本发明提供了在包括人细胞的细胞中繁殖猴腺病毒的方法,所述细胞包括从人腺病毒分离的一种或多种基因产物。还提供了繁殖方法,其中猴腺病毒包含编码人腺病毒基因产物的核酸序列。本发明进一步提供了通过这种繁殖方法获得的猴腺病毒,包括复制缺陷型猴腺病毒。 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130407692980.html">Recombinant Glut1 adeno-associated virus vector construct and method for restoring Glut1 expression</a> <b>[P]</b> . <span> 外国专利: <!-- 日本专利: --> JP2018509164A </span> <span> . 2018-04-05</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:重组glut1腺相关病毒载体的构建及恢复glut1表达的方法 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130447841215.html">Adeno-associated virus vector and cis-acting regulatory and promoter elements capable of expressing at least one gene and method of using same for gene therapy</a> <b>[P]</b> . <span> 外国专利: <!-- 美国专利: --> US6268213B1 </span> <span> . 2001-07-31</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:能够表达至少一种基因的腺相关病毒载体及顺式调控元件和启动子元件以及将其用于基因治疗的方法 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> 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