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Lego-Like Gene Editing Tool Lets Researchers Improve Cancer Immunotherapy

In recent years, scientists have used gene modification technologies to reprogram immune cells into therapeutics that can attack cancers. But such immunotherapies don’t work for all patients or all cancer types, and screening through every possible combination of genetic changes that might improve these reprogrammed immune cells is a daunting and slow task.

Now, scientists at Gladstone Institutes and UC San Francisco (UCSF) have developed a technology that lets them rapidly “snap” together thousands of different combinations of genetic edits to test in immune cells. They used their screening technology, called Modular Pooled Knockin Screening (ModPoKI), to identify a new combination of genes that, when added to immune cells, makes the cells last longer and become more effective at fighting cancers.

“This is a major step forward in our ability to ask questions about how we put pieces of genetic programs together into cells and test how they may be advantageous for patients,” says Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology and senior author of the new study published in Cell. “I think this is going to accelerate the development of better cellular therapies.”

“This study demonstrates the power of using high-throughput genomics to discover and engineer novel molecular programs in cell therapies, and further, to understand the impact of these programs on the T cell state that is required for cancer killing,” adds Ansuman Satpathy, MD, PhD, affiliate investigator at Gladstone, assistant professor in the Department of Pathology at the Stanford School of Medicine, and co-author of the study.



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