CRISPR-based gene editing enables <i>FOXP3</i> gene repair in IPEX patient cells
Marianne Goodwin, E. Lee, Uma Lakshmanan, Suzette Shipp, Luise Froessl, Federica Barzaghi, Laura Passerini, Mansi Narula, Adam Sheikali, Ciaran M. Lee, Gang Bao, Cindy S. Bauer, Holly Miller, Maria Garcia-Lloret, Manish J. Butte, Alice Bertaina, Ami J. Shah, Mara Pavel-Dinu, Ayal Hendel, Matthew H. Porteus, Maria‐Grazia Roncarolo, Rosa Bacchetta
Abstract
) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.