# Base editing of ASGR1 for cardiovascular disease

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $237,750

## Abstract

PROJECT SUMMARY
Heart diseases are the number one leading cause of death in the United States and worldwide, responsible for
over 655,000 American deaths each year. The most prevalent cardiovascular diseases (CVD) such as
coronary artery disease (CAD) arise from the interplay between complex genetic variants and environmental
factors. In particular, the low-density lipoproteins (LDL) is critical contributing factor to atherosclerosis and
increased risk of CVD. The use of statin drugs considerably reduced the incidence of CVD. Despite the
enormous progress of clinical practice in the past 30 years, insufficient LDL-cholesterol reduction and relatively
high residual risk remains for a significant proportion of statin-treated patients with or without combination
therapy, likely due to persistent relatively high triglyceride (TG) levels. This underscores the need for additional
new therapies targeting lipid metabolism in CVD prevention and treatment. Recent advances in genome
editing technologies, in particular the base editors, empower us to explore the feasibility of precise correction of
genetic mutations for genetic cardiomyopathy such as Duchenne muscular dystrophy (DMD). In a mouse
model of DMD, we recently achieved a near complete dystrophin restoration in the heart after a systemic
delivery of adenine base editor and the gRNA with adeno-associated virus 9 (AAV9). Leveraging this exciting
advancement in the in vivo base editing technology, here we will develop more broadly applicable therapeutic
strategies to combat CVD in a “hit-and-run” fashion (a technology we referred to as diBE), thus minimizing the
potential risks associated with AAV-mediated persistent expression of base editing reagents, which are known
to have intrinsic off-target DNA and RNA editing activities. We will determine the therapeutic potential of diBE-
mediated silencing of Asgr1 for protection against high fat diet induced hypercholesterolemia and
atherosclerosis in mice. Completion of these studies will have a high potential for making a major impact on the
development of novel base editing therapies to treat hyperlipidemia and CVD.

## Key facts

- **NIH application ID:** 10829341
- **Project number:** 5R21HL163720-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Renzhi Han
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $237,750
- **Award type:** 5
- **Project period:** 2023-04-17 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829341

## Citation

> US National Institutes of Health, RePORTER application 10829341, Base editing of ASGR1 for cardiovascular disease (5R21HL163720-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10829341. Licensed CC0.

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