Single Gene Knockout Strips Lab-Grown Heart Cells of Immune Visibility

Researchers in Japan report lab-grown heart cells that largely avoid immune detection by turning off a single gene. In a study published in iScience, a team led by Shugo Tohyama of Fujita Health University used CRISPR-Cas9 to disrupt TAPBP, which encodes tapasin and is needed to display HLA class I proteins on cell surfaces. Cardiomyocytes derived from human induced pluripotent stem cells showed markedly reduced HLA class I expression and evaded killing by cytotoxic T cells in lab tests. The approach did not trigger a natural killer cell response that has disrupted earlier hypoimmunogenic cell lines, addressing a key barrier to off-the-shelf cardiac therapies.