...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>PLoS Genetics >Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations
【24h】

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations

机译：新型CRISPR / Cas9基因驱动构建体揭示了遗传多样性人群中抗性等位基因形成机制和驱动效率的见解

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance. Although CRISPR gene drive activity has already been demonstrated, a key obstacle for current systems is their propensity to generate resistance alleles, which cannot be converted to drive alleles. In this study, we developed two CRISPR gene drive constructs based on the nanos and vasa promoters that allowed us to illuminate the different mechanisms by which resistance alleles are formed in the model organism Drosophila melanogaster. We observed resistance allele formation at high rates both prior to fertilization in the germline and post-fertilization in the embryo due to maternally deposited Cas9. Assessment of drive activity in genetically diverse backgrounds further revealed substantial differences in conversion efficiency and resistance rates. Our results demonstrate that the evolution of resistance will likely impose a severe limitation to the effectiveness of current CRISPR gene drive approaches, especially when applied to diverse natural populations.
机译：一个功能正常的基因驱动系统可以通过促进防止病原体传播或减少载体能力的转基因的快速传播，从根本上改变我们控制媒介传播疾病的策略。 CRISPR / Cas9基因驱动有望实现这种机制，其原理是将对驱动构建体杂合的细胞转化为纯合子，从而实现超孟德尔遗传。尽管已经证明了CRISPR基因驱动活性，但是当前系统的主要障碍是它们倾向于产生抗性等位基因，而这些抗性等位基因不能转化为驱动等位基因。在这项研究中，我们开发了两种基于nanos和vasa启动子的CRISPR基因驱动构建体，这使我们能够阐明在模型生物果蝇中形成抗性等位基因的不同机制。由于母体沉积的Cas9，我们在种系受精之前和胚胎受精后都观察到了高比率的抗性等位基因形成。遗传多样性背景下驱动活性的评估进一步揭示了转化效率和耐药率的显着差异。我们的结果表明，耐药性的进化可能会严重限制当前CRISPR基因驱动方法的有效性，尤其是当应用于多种自然种群时。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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