Epithelial-Mesenchymal Transition (EMT) is a complex and tightly regulated cellular process that involves profound phenotypic change in cells critical for embryonic development, tissue repair, and cancer progression. The RNA binding protein Quaking (QKI) regulates widespread changes in Alternative Splicing (AS) during EMT that directly impact cellular processes such as cell migration and invasion. However, despite the importance of AS for EMT, the functions of most alternatively spliced proteins are unknown due to challenges in manipulating AS in a scalable manner. We have catalogued ~500 AS events that are conserved across datasets related to EMT in both developmental processes and cancer. Using CRISPR technology, we are developing both DNA and RNA targeting modalities (Cas9 and dCas13d) to manipulate these conserved AS events and perform functional screens. In one example, deletion of exon 3 of the transcription factor NFYA – an exon strongly included as cells undergo EMT – results in a profound reduction in the migratory capacity of mesenchymal cells. We anticipate that these AS manipulating technologies will unveil functions of uncharacterised AS events for the first time and may pave the way for innovative strategies to manipulate EMT for therapeutic benefit.