Strategies for Genetically Engineering Hypoimmunogenic Universal Pluripotent Stem Cells

Abstract Despite progress to develop cell therapies, such as T cell or stem cell therapies to treat diseases, immuno-incompatibility remains a major barrier to clinical application. Given a host's immune system may reject allogeneic transplanted cells, methods have been developed to genetically modify patients' primary cells. To advance beyond this time-consuming and costly approach, recent research efforts focus on generating universal pluripotent stem cells to benefit a broader spectrum of patients. In this review, we first summarize current achievements to harness immunosuppressive mechanisms in cells to reduce immunogenicity. Then, we discuss several recent studies demonstrating the feasibility of genetically modifying pluripotent stem cells to escape immune attack and summarize the methods to evaluate hypoimmunogenicity. Though challenges remain, progress to develop genetically-engineered universal pluripotent stem cells holds the promise of expediting their use in future gene and cell therapeutics and regenerative medicine.