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基于 CRISPR-Cas9 的基因编辑在类器官中研究结直肠癌和肝癌发病机制的应用。

Application of CRISPR-Cas9 based gene editing to study the pathogenesis of colon and liver cancer using organoids.

机构信息

Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, D1 Block, Vasant Kunj, Delhi, 110070, India.

出版信息

Hepatol Int. 2021 Dec;15(6):1309-1317. doi: 10.1007/s12072-021-10237-z. Epub 2021 Oct 1.

Abstract

Two breakthrough techniques that have totally revolutionized biology in last 1 decade are the discovery of genome editing tools and growing the stem cells/primary tissue explants in defined 3D culture. In this regard the discovery of CRISPR-Cas9 as a specific gene editing tool and organoid culture from adult stem cell has provided easy handy tools to uncover the process of organ development and also modeling cancer. Genetically modified organoids have been developed by sequential knockout and knockin of driver mutations by genome editing followed by niche-based selection. The modified organoids when xenotransplanted in animal models faithfully recapitulate the neoplastic events of human tumors. The present review focuses on the merging of these two powerful technologies in understanding the complexities of colon and liver cancer.

摘要

在过去的 10 年中,有两项突破性技术彻底改变了生物学领域,它们分别是基因组编辑工具的发现和在定义的 3D 培养中培养干细胞/原代组织外植体。在这方面,CRISPR-Cas9 作为一种特定的基因编辑工具的发现和从成体干细胞中培养类器官,为揭示器官发育过程以及癌症建模提供了简单易用的工具。通过基因组编辑进行顺序敲除和敲入驱动突变,已经开发出了基因修饰的类器官,然后进行基于小生境的选择。当将修饰的类器官异种移植到动物模型中时,它们忠实地再现了人类肿瘤的肿瘤发生事件。本综述重点介绍了这两种强大技术的融合,以了解结肠癌和肝癌的复杂性。

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