Breakthrough Technique for T Cell Engineering

GENETIC REPROGRAMMING of human T cells without the use of a virus has successfully been achieved, marking a significant breakthrough for the field of cell therapy and treatment of immunological diseases. Using a new, non-viral, ‘cut and paste’ CRISPR system to edit the genome sequences, fast and specific changes were made to T cell DNA sequences, providing hope for new gene and cell therapies.

While viruses have previously been used to engineer T cells, the process can be long and can result in dangerous gene modifications, causing concern that there may be serious side effects. A team based at the University of California, San Francisco (UCSF), San Francisco, California, USA, have, therefore, been investigating the use of specific ratios of T cells, DNA, and CRISPR components, combined with an electrical field, to more accurately edit T cell genomes.

To test the versatility and power of this method of genome editing, the team studied T cells with mutations in IL2RA, a gene crucial in the development of regulatory T cells and vital for preventing autoimmunity. In children with this mutation, the method was successfully used to repair the defect and restore cellular signals. Furthermore, the non-viral CRISPR method was also able to reprogram T cells to display a new type of T cell receptor, creating cells with specific anti-cancer activity for a particular subtype of human melanoma cells.

Furthermore, not only is this technique fast and easy to use, it also allows large DNA stretches to be inserted into T cells, leading to new cellular properties. “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, recognise infections, or tamp down the excessive immune response seen in autoimmune disease”, commented study senior author Prof Alex Marson, UCSF. The team also noted that the ground-breaking results shown using this new technique will revolutionise research, as genome engineering investigations that were once considered challenging or costly with viral vectors are now easier to perform. It is hoped that the new technology will now be widely adopted by the field of cell therapy, enabling the acceleration of the development of safer treatments for cancer, autoimmunity, and other immunological disorders.