Considerations and practical implications of performing a phenotypic CRISPR/Cas survival screen

• DOI: 10.1371/journal.pone.0263262
• Publication Date: 2022-02-17T18:43:18Z
• Authors: Ator Ashoti; Francesco Limone; Melissa van Krane...; Anna Alemany; Mirna Baak; Judith Vivié; Frederica Piccioni; Pascale F. Dijkers; Menno Creyghton; Kevin Eggan; Niels Geijsen
• Keywords: Facioscapulohumeral muscular dystrophy

Genome-wide screens that have viability as a readout been instrumental to identify essential genes. The development of gene knockout with the use CRISPR-Cas has provided more sensitive method these Here, we performed an exhaustive genome-wide CRISPR/Cas9 phenotypic rescue screen modulators cytotoxicity induced by pioneer transcription factor, DUX4. Misexpression DUX4 due failure in epigenetic repressive mechanisms underlies facioscapulohumeral muscular dystrophy (FHSD), complex muscle disorder thus far remains untreatable. As name implies, FSHD generally starts muscles face and shoulder girdle. Our revealed no key effectors other than itself could modulate cytotoxicity, suggesting treatment efforts should be directed towards direct modulation itself. did however reveal some rare unexpected genomic events, had important impact on interpretation our data. findings may provide considerations for planning future survival screens.