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Genome engineering has the potential to revolutionize medicine. The modularity of CRISPR enables high-throughput functional assessment of genomic regions, providing insights into the regulation of cellular processes and identifying potential therapeutic targets.
This webcast will describe how building CRISPR screening platforms in primary human T cells helps reveal regulators of central T cell functions, including cytokine production, surface marker regulation, and cytotoxic activity with potential therapeutic application.
In detail, this new work first employed genome-wide CRISPR activation and CRISPR interference, mapping regulators of T cell cytokine production, which included targets for cancer cell therapies. In a next step, base editing increased screening resolution from gene to nucleotide level and identified loss- and gain-of-function alleles that shaped T cell functionality.
Projecting those mutations onto the two- and three-dimensional protein space allowed identification of functional regions within those genes and the generation of allelic series to fine-tune T cell activity. Together, these studies aimed to provide insights into genetic determinants of T cell functions and help inform the design of next-generation genome therapies in T cells.
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