• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Molecular Therapy. Nucleic Acids >Base editing strategy for insertion of the A673T mutation in the APP gene to prevent the development of AD
【2h】

Base editing strategy for insertion of the A673T mutation in the APP gene to prevent the development of AD

机译：在APP基因中插入A673T突变的基本编辑策略以防止广告的发展

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The amyloid precursor protein (APP) is a transmembrane protein mostly found in neurons. Cleavage of this protein by β-secretase can lead to the formation of amyloid-β (Aβ) peptide plaque, which leads to Alzheimer’s disease. Genomic analysis of an Icelandic population that did not show symptoms of Alzheimer’s at an advanced age led to the discovery of the A673T mutation. This mutation can reduce β-secretase cleavage by 40%. We hypothesized that the insertion of this mutation in patients’ neurons could be an effective and sustainable method of slowing down or even stopping the progression of Alzheimer’s disease. We modified the APP gene in HEK293T cells and in SH-SY5Y neuroblastoma using a Cas9 nickase (Cas9n)-deaminase enzyme to convert the alanine codon to a threonine. Several Cas9n-deaminase variants were tested to compare their efficiency of conversion. The results were characterized and quantified by deep sequencing. We successfully introduced the A673T mutation in 53% of HEK293T cells alongside a new mutation (E674K), which seemed to further reduce Aβ peptide accumulation. Our approach aimed to provide a new strategy for the treatment of Alzheimer’s and in so doing, demonstrate the capacity of base editing techniques for treating genetic diseases.
机译：淀粉样蛋白前体蛋白（APP）是在神经元中发现的跨膜蛋白。通过β-分泌酶切割该蛋白质可以导致形成淀粉样蛋白-β（Aβ）肽斑块，这导致阿尔茨海默病。冰岛种群的基因组分析，没有显示阿尔茨海默氏症在高级年龄的症状导致了A673T突变的发现。该突变可以将β-分泌酶切割减少40％。我们假设这种突变在患者的神经元中的插入可能是减缓甚至停止阿尔茨海默病进展的有效和可持续的方法。我们在HEK293T细胞和SH-SY5Y神经母细胞瘤中修饰了APP基因，使用CAS9酸酐（CAS9N） - 酵母酶将丙氨酸密码子转化为苏氨酸。测试了几种Cas9N-脱氨酶变体以比较它们的转化效率。通过深度测序表征和量化结果。我们在新的突变（E674K）旁，我们成功地引入了53％的HEK293T细胞中的A673T突变，似乎进一步降低了Aβ肽积累。我们的方法旨在为Alzheimer的治疗提供新的策略，因此表明了治疗遗传疾病的基础编辑技术的能力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号