posted on 2024-09-03, 07:20authored byJu-Fang Chang, Nils Wellhausen, Nils W. Engel, Jack H. Landmann, Caitlin R. Hopkins, January Salas-McKee, Adham S. Bear, Mehmet E. Selli, Sangya Agarwal, Julie K. Jadlowsky, Gerald P. Linette, Saar Gill, Carl H. June, Joseph A. Fraietta, Nathan Singh
A, Representative ow cytometry plots of transduction efficiency of various synthetic receptors in control (unedited) and TRAC+TRBCKO T cells when editing is performed pre-stimulation. B, Stability of CRISPR editing over-time when performing post-stimulation editing.
History
ARTICLE ABSTRACT
Genome editing technologies have seen remarkable progress in recent years, enabling precise regulation of exogenous and endogenous genes. These advances have been extensively applied to the engineering of human T lymphocytes, leading to the development of practice changing therapies for patients with cancer and the promise of synthetic immune cell therapies for a variety of nonmalignant diseases. Many distinct conceptual and technical approaches have been used to edit T-cell genomes, however targeted assessments of which techniques are most effective for manufacturing, gene editing, and transgene expression are rarely reported. Through extensive comparative evaluation, we identified methods that most effectively enhance engineering of research-scale and preclinical T-cell products at critical stages of manufacturing.