Targeting Cis-Regulatory Elements in β-Hemoglobinopathies: Advances in Gene Editing, RNA Therapeutics, and Epigenetic Modulation

Tianyi Xia

2025

Abstract

β-hemoglobinopathies, including sickle cell disease and β-thalassemia, are debilitating genetic disorders caused by mutations in the Hemoglobin Subunit Beta (HBB) gene or its cis-regulatory elements (CREs). These conditions disrupt hemoglobin synthesis, leading to chronic anemia, ineffective erythropoiesis, and multi-organ damage. Recent advances in CRISPR/Cas9-based gene editing, RNA therapeutics, and epigenetic modulation have revolutionized therapeutic strategies by targeting CREs such as the β-globin locus control region and γ-globin promoters. For instance, CRISPR-mediated disruption of the BCL11A enhancer reactivates fetal hemoglobin in adult erythrocytes, achieving transfusion independence in 95% of β-thalassemia patients. Similarly, base editing and antisense oligonucleotides (ASOs) offer precise correction of mutations or transient modulation of CRE activity, though challenges such as off-target effects, delivery inefficiency, and genetic heterogeneity persist. This article reviews current knowledge on the cis-regulatory mechanisms governing HBB expression, evaluates emerging therapeutic approaches, and highlights unresolved challenges, providing a guideline for the future direction of the following research.

Paper Citation

in Harvard Style

Xia T. (2025). Targeting Cis-Regulatory Elements in β-Hemoglobinopathies: Advances in Gene Editing, RNA Therapeutics, and Epigenetic Modulation. In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science - Volume 1: BEFS; ISBN 978-989-758-789-4, SciTePress, pages 144-148. DOI: 10.5220/0014436800004933

in Bibtex Style

@conference{befs25,
author={Tianyi Xia},
title={Targeting Cis-Regulatory Elements in β-Hemoglobinopathies: Advances in Gene Editing, RNA Therapeutics, and Epigenetic Modulation},
booktitle={Proceedings of the 1st International Conference on Biomedical Engineering and Food Science - Volume 1: BEFS},
year={2025},
pages={144-148},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0014436800004933},
isbn={978-989-758-789-4},
}

in EndNote Style

TY - CONF

JO - Proceedings of the 1st International Conference on Biomedical Engineering and Food Science - Volume 1: BEFS
TI - Targeting Cis-Regulatory Elements in β-Hemoglobinopathies: Advances in Gene Editing, RNA Therapeutics, and Epigenetic Modulation
SN - 978-989-758-789-4
AU - Xia T.
PY - 2025
SP - 144
EP - 148
DO - 10.5220/0014436800004933
PB - SciTePress