In an achievement that has significant implications for research, medicine, and industry, UC San Francisco scientists have genetically reprogrammed the human immune cells known as T cells without using viruses to insert DNA. The researchers said they expect their technique—a rapid, versatile, and economical approach employing CRISPR gene-editing technology—to be widely adopted in the burgeoning field of cell therapy, accelerating the development of new and safer treatments for cancer, autoimmunity, and other diseases, including rare inherited disorders.
The new method, described in the July 11, 2018 issue of Nature, offers a robust molecular "cut and paste" system to rewrite genome sequences in human T cells. It relies on electroporation, a process in which an electrical field is applied to cells to make their membranes temporarily more permeable. After experimenting with thousands of variables over the course of a year, the UCSF researchers found that when certain quantities of T cells, DNA, and the CRISPR "scissors" are mixed together and then exposed to an appropriate electrical field, the T cells will take in these elements and integrate specified genetic sequences precisely at the site of a CRISPR-programmed cut in the genome.
"This is a rapid, flexible method that can be used to alter, enhance, and reprogram T cells so we can give them the specificity we want to destroy cancer, recognize infections, or tamp down the excessive immune response seen in autoimmune disease," said UCSF's Alex Marson, MD, Ph.D., associate professor of microbiology and immunology, member of the UCSF Helen Diller Family Comprehensive Cancer Center, and senior author of the new study. "Now we're off to the races on all these fronts."
