Whole-genome CRISPR screening has revolutionised functional genomics. It can identify genes regulating a variety of cellular functions including cancer growth, cell differentiation or immunity. However, current CRISPR libraries target one gene at a time and are thus severely limited by functional compensation by redundant genes. Gene redundancy is common in higher organisms and creates large “gaps” in the screening results, which prevents the delineation of meaningful biological pathways. This project aims to systematically address the gene-redundancy problem by developing dual and triple-gene targeting CRISPR libraries focused on computationally identified paralogues, the largest class of redundant genes.
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