Effect of JV001 genetic therapy on gene expression during transverse aortic constriction (TAC) and angiotensin II (Ang II) induced heart failure.

Telomeric ends are capped to prevent activation of DNA damage response by the shelterin complex. To design a gene therapy that recap telomeric ends, engineering of the telomerase protein was considered given its preference to bind 3’ overhang terminally. We designed a pan-HF gene therapy (the modified TERT, JV001) – that acts through telomeric reprotection and restore myocardial mitochondrial biogenesis – and validate safety and efficacy in heart failure murine models. Heart failure were induced with the TAC surgery and the use of Ang II, and the study about either of the two models of heart failure consisted of three groups: control group, heart failure group, heart failure with JV001 treatment group. The control group standed for mice receiving sham surgery in the TAC study, and mice receiving saline infusion in the Ang II study. The heart failure group induced with either TAC or Ang II were injected with empty vector, for the comparison with the JV001 group. After the experiment, we employed RNA-sequencing to analyze the cardiomyocytes from the mouse models.