利用CRISPR-Cas9基因编辑技术,在HD敲入小鼠模型中进行体内筛选,系统性鉴定CAG重复不稳定性的遗传修饰因子,并探索潜在的治疗靶点。 研究方法 HD敲入小鼠模型 :使用HttQ111敲入小鼠,这是研究HTT CAG扩展的优秀系统,能够模拟人类HD的病理特征。 CRISPR-Cas9体内筛选 :使用腺相关病毒(AAV)全身递送sgRNA,靶向HD发病修饰...
品系描述 通过C57BL/6-Gt(ROSA)26Sortm1(CAG-LNL-Cas9)Smoc(NM-KI-00038)与EIIA-Cre工具鼠交配得直接全身表达Cas9蛋白的小鼠。 应用领域:基因敲除、基因修饰 *使用本品系发表的文献需注明: R26-CAG-Cas9 mice (Cat. NO. NM-KI-00120) were purchased from Shanghai Model Organisms Center, Inc.. ...
pCAG Cas9-2A-Citrine (Plasmid #92358) HH-CAS-160pU6-pegRNA-GG-acceptor(Plasmid #132777) HH-CAS-159pCMV-T7-ABEmax(7.10)-SpRY-P2A-EGFP (RTW5025)(Plasmid #140003) HH-CAS-157PB-TRE-dCas9-KRAB-MeCP2(Plasmid #122267) HH-CAS-158Lenti-eCas9(Plasmid #140237) HH-CAS-158 HH-CAS-...
图2 (C)代表性片段长度轨迹:基线(灰色);用载体(深蓝色)治疗15周;0.022 μM(浅蓝色)、0.26 μM(紫色)或3 μM MSH3 ASO(橙色)治疗15周;3 μM假ASO对照 (SCR,绿色)治疗15周。图2 (D)在HD 125 CAG iPSCs中,经过CRISPR-Cas...
We have previously demonstrated that the Cas9 D10A nickase can effectively contract CAG/CTG repeats when targeted to the repeat tract itself. However, the mechanism remains unclear. Here, we tested whether nickase-mediated contractions depend on transcription or on replication using human cell models...
为验证内源性TDP-43蛋白敲降所导致的MLH1和MSH3高表达是造成CAG重复序列不稳定性的增加的关键蛋白,作者又针对小鼠内源性MLH1和MSH3基因设计了CRISPR/Cas9基因编辑的引导gRNA(图3 A),在HD模型小鼠纹状体中直接敲低MLH1或MSH3的基因表达,来观察其对CAG重复序列不稳定性的影响。PCR电泳检测(图3 B)及第三代高通量PCR...
pCAG Cas9-2A-Citrine质粒 货号:#92358-20ul 货号产品名称规格库存价格数量购买 #92358-20ulpCAG Cas9-2A-Citrine质粒20ul 立即咨询 +- 产品介绍 相关产品 》产品信息 货号名称规格 #92358pCAG Cas9-2A-Citrine质粒 20ul 》产品描述 基因编辑 》产品简介 ...
为验证内源性TDP-43蛋白敲降所导致的MLH1和MSH3高表达是造成CAG重复序列不稳定性的增加的关键蛋白,作者又针对小鼠内源性MLH1和MSH3基因设计了CRISPR/Cas9基因编辑的引导gRNA(图3 A),在HD模型小鼠纹状体中直接敲低MLH1或MSH3的基因表达,来观察其对CAG重复序列不稳定性的影响。PCR电泳检测(图3 B)及第三代高通量PCR...
(that is, relevance to in vivo instability in tissues) can be unclear. To bridge this gap, and with the goal of better understanding the factors and pathways that underlie somatic expansion, we have established an in vivo CRISPR–Cas9-based system for identifying somaticHTTCAG expansion-modifier...
A single intracranial or intravenous injection of adeno-associated virus encoding for Cas9, a single-guide RNA targeting the HTT gene, and donor DNA containing the normal CAG repeat led to the depletion of mutant HTT in the animals and to substantial reductions in the dysregulated expression and ...