Grant Award Details

Modified RNA-Based Gene Therapy for Cardiac Regeneration Through Cardiomyocyte Proliferation
Grant Number: 
DISC2-13512
Project Objective: 
  • To determine if simultaneous delivery of modified RNA (modRNA) encoding 4 cyclin associated genes (CDK1, CDK4, CCNB1 and CCND1, collectively 4F) delivered in lipid nanoparticles (LNP) via intramyocardial injection promotes regeneration of the heart in congestive heart failure. (Therapeutic candidate: 4F modRNA LNP)
Investigator: 
Type: 
PI
Disease Focus: 
Heart Disease
Heart failure
Human Stem Cell Use: 
iPS Cell
Award Value: 
$1,565,784
Status: 
Pre-Active

Grant Application Details

Application Title: 
  • Modified RNA-Based Gene Therapy for Cardiac Regeneration Through Cardiomyocyte Proliferation
Public Abstract: 

Research Objective

Efficacious and safe intramyocardial delivery of modified mRNA encoding cell cycle regulators as a gene therapy for cardiac regeneration through resident cardiomyocyte proliferation.

Impact

This project would provide disease-modifying gene therapy for people with heart failure due to loss of cardiac muscle, a leading cause of deaths in the US, using novel modified mRNA delivery.

Major Proposed Activities

  • Human iPS-derived cardiomyocytes successfully transduced with modified RNA (modRNA) encoding human cell cycle regulators.
  • Successful delivery of modRNA encoding cell cycle regulators into mouse hearts
  • Successful stimulation of human cardiomyocyte division in a dish and adult mouse cardiomyocytes in vivo with modRNA delivery of cell cycle regulators
  • Efficacy of modRNA delivery of cell cycle regulators on improving ejection fraction in mice with acute myocardial infarction (MI).
  • Efficacy of modRNA delivery of cell cycle regulators on improving cardiac function in chronic post-MI rats.
  • Evaluate safety parameters for modRNA delivery of cell cycle regulators in mice and rats.
Statement of Benefit to California: 

Heart disease is a leading cause of mortality and end-stage heart failure carries a 50% two-year mortality. Few treatments are available and even those do not alter the basis for disease, resulting in ultimate need for heart transplant. We propose gene delivery mediated by modified mRNA, as used in COVID vaccines, to reprogram adult cardiomyocytes transiently into a proliferative state for cardiac regeneration, thereby improving heart function.