Name:
Institution:
Type:
PI
Grant Award Details
Novel Lipid Nanoparticles for Enhancing eNOS Synthesis for Cardioprotection Post Myocardial Infarction
Grant Type:
Grant Number:
DISC2-14045
Project Objective:
- To develop and test a lipid nanoparticle (LNP)-delivered mRNA gene therapy candidate encoding endothelial nitric oxide synthase (eNOS) as a cardioprotective treatment post myocardial infarction (MI)
Investigator:
Disease Focus:
Heart Disease
Heart failure
Human Stem Cell Use:
iPS Cell
Award Value:
$2,060,248
Status:
Pre-Active
Grant Application Details
Application Title:
- Novel Lipid Nanoparticles for Enhancing eNOS Synthesis for Cardioprotection Post Myocardial Infarction
Public Abstract:
Research Objective
Our therapeutic candidate is a lipid nanoparticle that delivers a therapeutic dose of mRNA to the human heart, which transiently transfects of cells within the heart to improve function after an MI.
Impact
There is evidence for eNOS therapy as a cardioprotectant post MI; however, the progression of to the clinic has stalled due to inadequate delivery systems. Our therapeutic addresses this bottleneck.
Major Proposed Activities
- Optimize PEGylated LNPs that edit heart muscle derived from XR1-iCMs. To achieve this goal, we will synthesize new lipids that increase diffusivity in the heart micromuscle derived from hiPSC.
- Assess endogenous NO synthesis via eNOS mRNA delivered to heart micromuscles constructed from various patient lines. Deliverable is at least 5 LNPs to be evaluated in Milestone 3.
- PEGylated LNP-induced expression in infarcted Ai6 mice. Deliverable is at least one LNP for optimal mRNA delivery into an infarcted heart with minimal toxicity that we will test in Milestone 5.
- Develop LNPs that target coronary artery endothelial cells (aECs). Deliverable is at least one EC targeted LNP for evaluation in Milestone 5.
- Efficacy of eNOS mRNA LNPs on improving cardiac function in mice with acute MI. Deliverable is a eNOS mRNA LNP therapeutic for the cardioprotection of mice after acute myocardial infarction.
Statement of Benefit to California:
Heart failure (HF) is a common human disease; after 40 years of age, the lifetime risk of developing heart failure is 20% for both women and men. The disparity of HF amongst various racial and ethnic US populations is also well documented. Our therapeutic candidate is a lipid nanoparticle that delivers a therapeutic dose of mRNA to the human heart to improve function after a heart attack. If successful, then our therapeutic would provide needed therapy for millions of Californians.
