利用多重细胞系筛选平台对癌症脆弱性进行遗传和药理学研究。

Genetic and pharmacological interrogation of cancer vulnerability using a multiplexed cell line screening platform.

机构信息

Bristol Myers Squibb, San Diego, CA, USA.

出版信息

Commun Biol. 2021 Jul 2;4(1):834. doi: 10.1038/s42003-021-02352-2.

DOI:10.1038/s42003-021-02352-2

PMID:34215850

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8253734/

Abstract

The multiplexed cancer cell line screening platform PRISM demonstrated its utility in testing hundreds of cell lines in a single run, possessing the potential to speed up anti-cancer drug discovery, validation and optimization. Here we described the development and implementation of a next-generation PRISM platform combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated gene editing, cell line DNA barcoding and next-generation sequencing to enable genetic and/or pharmacological assessment of target addiction in hundreds of cell lines simultaneously. Both compound and CRISPR-knockout PRISM screens well recapitulated the results from individual assays and showed high consistency with a public database.

摘要

多重癌细胞系筛选平台 PRISM 展示了其在单次运行中测试数百种细胞系的效用，具有加速抗癌药物发现、验证和优化的潜力。在这里，我们描述了一种结合 CRISPR/Cas9 介导的基因编辑、细胞系 DNA 条码和下一代测序的下一代 PRISM 平台的开发和实施，以实现同时对数百种细胞系中的靶标成瘾进行遗传和/或药理学评估。化合物和 CRISPR 敲除 PRISM 筛选都很好地再现了单个测定的结果，并与公共数据库高度一致。