Sonja Schrepfer, MD, PhD, Sana Biotechnology, Seattle, WA, explains the rationale behind the development of hypoimmunogenic induced pluripotent stem cells (iPSCs). Lessons learned from the fetal-maternal tolerance concept has led to the understanding that rejection of allogeneic iPSCs upon implantation can be prevented by knocking out human leukocyte antigen (HLA) molecules through gene editing, thus overcoming adaptive immunity. Simultaneous overexpression of CD47 is also required to prevent missing-self recognition by innate immune cells following HLA knockout, thus inhibiting natural killer (NK) cell and macrophage killing of the iPSCs. Various mouse models have been used to demonstrate the regenerative capacity of differentiated hypoimmunogenic iPSCs, as well as their potential application in chimeric antigen receptor (CAR) T-cell therapy for cancer. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.
Sonja Schrepfer is a scientific founder and stockholder of Sana Biotechnology, Inc. (“Sana”). Since Feb 2019, Sonja Schrepfer has been an employee of Sana in South San Francisco, CA, and since 2015, has been a Professor of Surgery at the University of California San Francisco (“UCSF”).