Scientific Advances: CRISPR screen identifies 105 gene combinations resulting in loss of cellular fitness

February 26, 2021.

From the labs of Stephen Jackson and David Adams, a study was published in Nature Communications in which the systematic disruption of 1191 gene pairs was analyzed. The authors focused on gene pairs, including paralogs, that evolved to provide genetic redundancy in order to safeguard essential cellular processes. However, genetic redundancy is also critical for the survival of malignant cells in light of their mutation loads and abnormal karyotypes. Overall, 105 unique gene combinations were identified that reduced cellular fitness after co-disruption, with 27 combinations inducing synthetic sickness across multiple tumor cell lines. Among these consistent hits were two paralogs of unknown function: FAM50A/FAM50B. This offers potentially a new therapeutic approach against cancer based on synthetic lethality as FAM50B silencing has been documented in various malignancies.  

For more information, see: Thompson, N.A., et al. (2021) Combinatorial CRISPR screen identifies fitness effects of gene paralogues. Nat. Commun. 12, 1302.

Keywords: CRISPR screen, Synthetic lethality, FAM50

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