# CRISPR-induced cardiovascular progenitor cells to repair myocardial infarction

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2022 · $547,786

## Abstract

Project Summary/Abstract
Cardiovascular disease associated with myocardial infarction (MI) remains a major cause of death
worldwide. Cell reprogramming into cardiovascular progenitor cells (CPCs), bypassing the process of
pluripotency induction, has provided a promising approach for cardiac repair through simultaneous
neovascularization and cardiomyogenesis. One significant gap in current research is an unclear
understanding of the mechanisms of direct reprogramming. The activation of endogenous genetic loci
(that are occluded by repressive chromatin marks) in starting cells has been considered an important
criterion of high-quality fully reprogrammed cells. Therefore, we attempt to obtain a new source of CPCs
through direct manipulation of endogenous genes. To this end, we propose a combined use of
reprogramming technologies and CRISPR-based tools. CRISPR-induced gene activation is superior to
conventional techniques employing cDNA overexpression due to its effectiveness, simplicity of design
and avoidance of the need for additional transduction of transcription factor complexes. Our preliminary
data demonstrates that CRISPR-induced cells possess the properties of CPCs including clonality, self-
renewal, and cardiac tri-potentiality. Importantly, the CRISPR-induced CPCs (iCPCs) can blunt the
worsening of heart function and reduce infarct size after transplantation in MI mice. These findings are
the basis for a further systematic investigation of CRISPR-iCPCs in a preclinical setting. Accordingly,
three Specific Aims are proposed to develop a technical platform to generate new CRISPR-iCPCs, study
cell-reprogramming mechanisms, and evaluate the application of iCPCs for MI therapy. In Aim-1, a new
non-viral CRISPR system will be developed for generation of iCPCs using a clinically acceptable gene
vector system and the biological and functional features of new iCPCs will be characterized. In Aim-2,
epigenetic factors mediating iCPC generation will be the focus of experiments. Long non-coding RNAs
and targeted epigenetic mediators will be investigated to dissect the mechanisms of cellular
reprogramming. In Aim-3, iCPCs will be implanted using cell patch techniques, and their cell fate
decisions will be tracked in the infarcted heart. The extent and role of differentiated iCPCs will be
determined by in vivo imaging and distinguished from other consequences using a cell ablation approach.
In conclusion, this proposal will provide a new regeneration strategy for MI therapy through convergence
of CRISPR technology and tissue engineering in CPC development.

## Key facts

- **NIH application ID:** 10372161
- **Project number:** 5R01HL157456-02
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Jialiang Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $547,786
- **Award type:** 5
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372161

## Citation

> US National Institutes of Health, RePORTER application 10372161, CRISPR-induced cardiovascular progenitor cells to repair myocardial infarction (5R01HL157456-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10372161. Licensed CC0.

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