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A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells.

ABSTRACT: Mapping genetic interactions in mammalian cells is limited due to technical obstacles. Here we describe a method called TCGI (tRNA-CRISPR for genetic interactions) to generate a high-efficient, barcode-free and scalable pairwise CRISPR libraries in mammalian cells for identifying genetic interactions. We have generated a genome- wide library to identify genes genetically interacting with TAZ in cell viability regulation. Validation of candidate synergistic genes reveals the screening accuracy of 85% and TAZ-MCL1 is characterized as combinational drug targets for non-small cell lung cancer treatments. TCGI has dramatically improved the current methods for mapping genetic interactions and screening drug targets for combinational therapies.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6787096 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells.

Zhao Yulei Y Tyrishkin Kathrin K Sjaarda Calvin C Khanal Prem P Stafford Jeff J Rauh Michael M Liu Xudong X Babak Tomas T Yang Xiaolong X

Scientific reports 20191010 1

Mapping genetic interactions in mammalian cells is limited due to technical obstacles. Here we describe a method called TCGI (tRNA-CRISPR for genetic interactions) to generate a high-efficient, barcode-free and scalable pairwise CRISPR libraries in mammalian cells for identifying genetic interactions. We have generated a genome- wide library to identify genes genetically interacting with TAZ in cell viability regulation. Validation of candidate synergistic genes reveals the screening accuracy of ...[more]

PMID: 31601883

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