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可预测和精确的无模板的CRISPR编辑病原体变异
Max W Shen1,2, Mandana Arbab3,4,5, Jonathan Y Hsu6,7
1Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature
|November 9, 2018
概括
没有模板的Cas9基因组编辑现在可以预测精确的DNA修复. 这种机器学习方法纠正了与疾病相关的突变,为基因治疗应用提供了新的工具.
科学领域:
- 基因组学
- 分子生物学
- 生物信息学
背景情况:
- 在Cas9分裂后的DNA修复通常是随机和不可预测的.
- 这限制了它的应用,不仅仅是基因破坏.
研究的目的:
- 为了证明可预测和精确的Cas9基因组编辑.
- 开发一个用于预测编辑结果的机器学习模型.
主要方法:
- 在2000个Cas9指导RNA和DNA目标点对上训练了一个机器学习模型.
- inDelphi可以预测删除和插入的基因型和频率.
- 在人类和小鼠细胞系中验证了预测.
主要成果:
- inDelphi准确地预测了编辑结果 (r=0.87).
- 在5-11%的病例中确定了Cas9指导RNA,产生精确的编辑 (精确-50).
- 成功纠正患者衍生细胞中的致病突变 (赫曼斯基- 普德拉克综合征,门克斯病).
结论:
- 没有模板的Cas9编辑可以精确和可预测.
- inDelphi可以准确地预测基因组编辑.
- 这种方法有助于精确纠正遗传疾病.
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