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bioRxiv · 10.1101/2023.11.15.567224

Pooled screening for biochemically-defined phenotypes using CRISPuRe-Seq

Harris, D. T.·Jan, C.
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Abstract

Phenotypic genetic screening is a powerful approach for biological discovery. CRISPR technologies have enabled routine genome-scale pooled perturbations in cultured cells, creating an opportunity to develop screening methods capable of accessing molecularly meaningful phenotypes. Here we present a generalized strategy, named CRISPuRe-seq, that enables pooled screening of a broad range of protein-based attributes. This approach utilizes the purification of an RNA-barcoded protein-of-interest to identify causative genetic perturbations. As a proof of concept, we screened for modifiers of Interferon alpha signaling and were able to identify all of the primary components of the type 1 Interferon JAK/STAT signaling pathway.

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Harris, D. T., Jan, C.. 2023-11-15. Pooled screening for biochemically-defined phenotypes using CRISPuRe-Seq. https://doi.org/10.1101/2023.11.15.567224

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