| abstract |
The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within the first exon of the human T cell receptor (TCR) alpha constant region gene. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced (i.e., increased) specificity or efficiency of cleavage, when compared to the first-generation meganuclease TRC l-2x.87EE. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating diseases, such as cancer. |