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

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 interaction...

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Detalles Bibliográficos
Autores principales: Zhao, Yulei, Tyrishkin, Kathrin, Sjaarda, Calvin, Khanal, Prem, Stafford, Jeff, Rauh, Michael, Liu, Xudong, Babak, Tomas, Yang, Xiaolong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787096/
https://www.ncbi.nlm.nih.gov/pubmed/31601883
http://dx.doi.org/10.1038/s41598-019-51090-3
Descripción
Sumario: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.

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