Page 52 - GTM-2-1

Global Translational Medicine

REVIEW ARTICLE
Adenine base editing as a promising therapy for

cardiovascular diseases

1†
1
3†
Luzi Yang 1,2† , Zihao Tao , Xiaoteng Ma , Xuanhui Zhang , Yuxuan Guo 1,2,4,5 *,
and Fei Gao 3*
1 Peking University Health Science Center, School of Basic Medical Sciences, Beijing, 100191, China
2 Peking University Institute of Cardiovascular Sciences, Beijing, 100191, China
3 Beijing Anzhen Hospital, Department of Cardiology, Capital Medical University, Beijing, 100029,
China
4 Ministry of Education Key Laboratory of Molecular Cardiovascular Science, Beijing, 100191, China
5 Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China

Abstract
Cardiovascular diseases (CVDs) are the leading causes of human death worldwide.
Genetic variants serve as the major risk factor for CVDs, with limited therapeutic
interventions in clinical practice. The recent surge of genome editing technologies
offers the hope to correct genetic variants and to cure genetic diseases. Among the
diverse genome editing tools, adenine base editors (ABEs) exhibit high efficiency,
high specificity, and low off-target effects, successfully entering a clinical trial and
† These authors contributed equally demonstrating the tremendous potential to transform modern cardiovascular
to this work. therapy. In this review, we summarize the basic knowledge about ABE, showcase
three hallmark studies using ABE to ameliorate or treat CVDs in experimental animals,
*Corresponding authors:
Yuxuan Guo and lastly discuss about the key technical concerns that should be addressed to
(guo@bjmu.edu.cn) achieve the full potential of ABEs in the future.
Fei Gao
(fgaomd@163.com)
Citation: Yang L, Tao Z, Ma X, Keywords: Adenine base editor; Cardiovascular disease; Gene therapy
et al., 2023, Adenine base
editing as a promising therapy for
cardiovascular diseases. Global
Transl Med, 2(1): 232.
https://doi.org/10.36922/gtm.232 1. Introduction
Received: October 25, 2022 Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality
Accepted: January 27, 2023 worldwide. Genomic variants, often in the form of single nucleotide variants (SNVs),
Published Online: February 14, 2023
are one of the major causes of CVDs [1-3] . In the past decade, many CVD-associated
Copyright: © 2023 Author(s). SNVs were discovered, thanks to the advancement in high-throughput sequencing
This is an Open Access article technologies . However, effective therapies for these diseases remain absent.
[4]
distributed under the terms of the
Creative Commons Attribution The recent emergence of the genome editing technology has provided an unprecedented
License, permitting distribution,
and reproduction in any medium, opportunity to treat CVDs. This technology was derived from the clustered regularly
provided the original work is interspaced short palindromic repeats (CRISPRs) system in prokaryotes [5,6] . The CRISPR
properly cited. repeats in the prokaryotic genome encode an array of small non-coding RNA called the
Publisher’s Note: AccScience CRISPR RNA (crRNA). crRNA together with trans-activating crRNA (tracrRNA) was
Publishing remains neutral with later engineered to form a single guide RNA (sgRNA) , which can direct the CRISPR-
[7]
regard to jurisdictional claims in
published maps and institutional associated (Cas) nucleases, such as Cas9, to bind to a specific DNA sequence that is
affiliations. base-paired by the crRNA. Next, the nuclease locally digests the DNA and creates a DNA

Volume 2 Issue 1 (2023) 1 https://doi.org/10.36922/gtm.232