CRI Scientist’s “Rosetta Stone” Tech Unlocks New Era

I wanted to share some very exciting news about Alex Marson, MD, PhD, who is part of an elite cohort of CRI-funded scientists called STARs (Scientists TAking Risks). Recently reported in the prestigious journal Science, Dr. Marson has developed a new and astonishingly efficient gene activation technology with the potential to power significant advances in cancer immunotherapy as well as autoimmune and infectious diseases.

Dr. Alex Marson. Photo by Anastasiia Sapon

In their latest publication, Dr. Marson and his team at the Gladstone-UCSF Institute of Genomic Immunology report their use of a modified version of the genomic engineering tool CRISPR to create a biological “Rosetta Stone”—a reference to the tablet that enabled linguists to translate ancient Egyptian hieroglyphs for the first time. Dr. Marson’s research likewise is helping scientists to crack the immune system’s genetic code in order to understand which genes control which immune cell functions. “Now we have a basic molecular language we can use to engineer a T cell to have very precise properties,” Dr. Marson noted in an interview.

In contrast to traditional CRISPR-based snipping or swapping of genetic code, Dr. Marson’s approach allows him to probe every gene in the human genome—more thoroughly and rapidly than previously possible—to discover which genes can be “turned on” or “turned off” to enhance the immune system’s power to destroy cancer. His team has used this approach, dubbed CRISPRa and CRISPRi, to activate or interfere with, respectively, nearly 20,000 genes in human T cells, including some genes that had not been identified previously.

This is the first study to successfully use CRISPRa for large-scale genome engineering in human immune cells taken directly from individuals.

This groundbreaking technology has widespread application across medical research and will reveal even deeper insights into genetically engineered immune cells that may lead to more effective cell therapy and other immunotherapy approaches to treating cancer.

Thank you for supporting our work to advance Dr. Marson’s research along with that of hundreds of other scientists around the world who are currently receiving CRI support—support made possible by our generous donors. Together we are making a real difference in the lives of cancer patients.

Read some of the recent news coverage about this important breakthrough from the Gladstone Institutes, Fierce Biotech, and Cosmos, and read our 2019 interview with Dr. Marson about his important research.

Citation: Schmidt R et al. CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science. 4 Feb 2022. 375;(6580).