CRISPR/Cas9 gene editing was applied to the study of clonal hematopoiesis and cardiovascular disease. Hematopoietic stem cells were infected with lentivirus expressing CRISPR/Cas9 and gRNA targeting Tet2 or Dnmt3a. Gene-edited cells were transplanted into irradiated mice. Mice harboring mutant hematopoietic cells showed greater deterioration in a heart failure model. Cover illustration by Ben Smith. See related article, page 335.