Breakthrough in T Cell engineering

UC San Francisco scientists have genetically reprogrammed the T cells, human immune cells, using CRISPR gene-editing technology and without using viruses to insert DNA. It is anticipated that this breakthrough will hasten the development of new and safer treatments for diseases including rare inherited disorders, cancer and autoimmunity. The method uses electroporation which applies an electrical field to cells to make their membranes more permeable for a short time. The UCSF researchers eventually 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.
Alex Marson, associate professor of microbiology and immunology, member of the UCSF Helen Diller Family Comprehensive Cancer Center, and senior author of the new study, said: “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. Now we’re off to the races on all these fronts.” Alex believes the success of this method is down to Roth’s “absolute perseverance” in the face of the widespread beliefs that viral vectors were necessary and that only small pieces of DNA could be tolerated by T cells. “Theo was convinced that if we could figure out the right conditions we could overcome these perceived limitations, and he put in a Herculean effort to test thousands of different conditions: the ratio of the CRISPR to the DNA; different ways of culturing the cells; different electrical currents. By optimizing each of these parameters and putting the best conditions together he was able to see this astounding result.”
Theo Roth, who designed and led the new study in Marson’s lab, said: “There has been thirty years of work trying to get new genes into T cells. Now there should no longer be a need to have six or seven people in a lab working with viruses just to engineer T cells, and if we begin to see hundreds of labs engineering these cells instead of just a few, and working with increasingly more complex DNA sequences, we’ll be trying so many more possibilities that it will significantly speed up the development of future generations of cell therapy.”