# Development of gene editing based therapy for cardiovascular diseases

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $717,344

## Abstract

PROJECT SUMMARY/ABSTRACT
Recent therapeutic advances considerably reduced the incidence of cardiovascular disease (CVD). The
contribution of low-density (LDL) and very low density (VLDL) lipoproteins is critical in atherogenesis.
Regardless the progress of clinical treatments in the past 30 years, for a significant proportion of statin-treated
patients, with or without combination therapy, insufficient LDL-C reduction and relatively high residual risk still
remain, likely associated with persistent relatively high triglyceride (TG) levels, thus limiting the benefits of
these therapies. This underscores the need for additional new therapies targeting lipid metabolism in CVD
prevention and treatment. In this proposal, we propose to develop genetic deficiency of ApoC3 through an
adeno-associated virus (AAV) mediated in vivo silencing of ApoC3 by Cas9 base editor (Cas9-BE) strategy
(AAV-Cas9-BE-ApoC3) to render protection against high cholesterol diet-induced hypercholesterolemia and
atherosclerosis in rabbits. Specifically, we will 1) develop AAV-Cas9-BE-ApoC3 in a preclinical model species,
the New Zealand White rabbits. We will determine the optimal targeting strategies using in vitro cultured rabbit
cells, followed by experiments to determine the optimal delivery parameters to achieve effective ApoC3 gene
knockout in rabbit hepatocytes; 2) evaluate the efficacy of AAV-Cas9-BE-ApoC3 using optimal conditions
determined in Aim 1 to knockout ApoC3 in rabbits; 3) conduct multiple-year evaluation of the safety of AAV-
Cas9-BE-ApoC3 in rabbits. Completion of these aims by leveraging new CRISPR/Cas9 technology to target
ApoC3 will provide compelling evidence to establish ApoC3 as a novel feasible target for gene editing-based
therapy for hyperlipidemia and CVD.

## Key facts

- **NIH application ID:** 10313701
- **Project number:** 1R01HL159900-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** YUQING Eugene CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $717,344
- **Award type:** 1
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313701

## Citation

> US National Institutes of Health, RePORTER application 10313701, Development of gene editing based therapy for cardiovascular diseases (1R01HL159900-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10313701. Licensed CC0.

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