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Simultaneous engineering of natural killer cells for CAR transgenesis and CRISPR-Cas9 knockout using retroviral particles by Dong-Hyeon Jo; Shelby Kaczmarek; Oksu Shin; Lisheng Wang; Juthaporn Cowan; Scott McComb; Seung-Hwan Lee is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Simultaneous engineering of natural killer cells for CAR transgenesis and CRISPR-Cas9 knockout using retroviral particles about?

Natural killer (NK) cells are potent cytotoxic innate lymphocytes that can be used for cancer immunotherapy. Since the balance of signals from activating and inhibitory receptors determines the activity of NK cells, their anti-tumor activity can be potentiated by overexpressing activating receptors or knocking out inhibitory receptors via genome engineering, such as chimeric antigen receptor (CAR) transgenesis and CRISPR-Cas9-mediated gene editing, respectively. Here, we report the development of a one-step strategy for CRISPR-Cas9-mediated gene knockout and CAR transgenesis in NK cells using retroviral particles. We generated NK cells expressing anti-epidermal growth factor receptor (EGFR)-CAR with simultaneous TIGIT gene knockout using single transduction and evaluated the consequence of the genetic modifications in vitro and in vivo. Taken together, our results demonstrate that retroviral particle-mediated engineering provides a strategy readily applicable to simultaneous genetic modifications of NK cells for efficient immunotherapy.

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Author

Dong-Hyeon Jo; Shelby Kaczmarek; Oksu Shin; Lisheng Wang; Juthaporn Cowan; Scott McComb; Seung-Hwan Lee

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)