精确的临床前癌症模型的生成,使用调节的体内基调编辑
Alyna Katti1,2, Adrián Vega-Pérez1, Miguel Foronda1,3
1Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Nature biotechnology
|August 10, 2023
概括
研究人员开发了一种诱导基编辑 (iBE) 鼠标模型,以研究单核酸变体 (SNV) 在癌症中的影响. 该系统允许在体内对基因编辑进行时间控制,从而可以创建临床前癌症模型.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 癌症研究 癌症研究
- 分子生物学分子生物学
背景情况:
- 单核酸变体 (SNVs) 在癌症中很常见,但它们对瘤开始和进展的功能影响在很大程度上是未知的.
- 现有的方法缺乏研究SNVs在体内随时间推移的特定影响的能力.
研究的目的:
- 开发一种新的小鼠系统,用于时间和可调节的体内基调编辑.
- 为了使癌症相关的SNV在临床前模型中的功能性询问.
主要方法:
- 开发一种可诱导基编辑 (iBE) 鼠标模型,具有多西环素依赖的细胞酸基编辑表达.
- 利用基于等离子体的或合成导向RNA用于有效的SNV工程器官 (肠道,肺部,胰腺).
- 证明了 ex vivo 和 in vivo 序列基因组编辑基因编辑器活动的时间调节.
- 通过直接将sgRNA传递到点组织,促进了在现场临床前癌症模型的生成.
主要成果:
- 通过iBE鼠标系统,可以在各种组织中进行强大的,依赖多西环林的基质编辑.
- 在肠道,肺部和胰腺器官中实现了单个和多个SNV的高效工程.
- 基因编辑的时间控制允许进行受控的,顺序的基因组修改.
- 在现场成功生成了临床前癌症模型.
结论:
- 诱导基编辑 (iBE) 鼠标系统为研究SNVs在癌症中的功能影响提供了强大的工具.
- 这项技术有助于创建复杂的,暂时控制的体内临床前癌症模型.
- 能够更深入地了解SNVs如何促进瘤发病和进展.
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