Page 70 - GPD-3-3

Gene & Protein in Disease

REVIEW ARTICLE
Advances and challenges in gene therapy for

dystrophic epidermolysis bullosa: Insights from
therapeutic strategies and animal models

1
2
1
Xianqing Wang 1,2 , Josie Ward 2 , Wei He , Wenxin Wang * , and Ming Li *
1 Department of Dermatology, Children’s Hospital of Fudan University, National Children’s Medical
Center, Shanghai, China
2 Charles Institute of Dermatology, School of Medicine, University College Dubin, Dublin, Ireland

Abstract

Dystrophic epidermolysis bullosa (DEB) is a severe monogenic skin disorder resulting
from mutations in the COL7A1 gene, which disrupts the synthesis of type VII
collagen. This leads to impaired anchoring fibrils and results in dermoepidermal
separation. The clinical manifestation of DEB varies significantly, ranging from
localized blistering in milder forms to extensive blistering with subsequent severe
complications such as vision loss and squamous cell carcinoma in more severe cases.
Despite the recent approval of the first gene replacement therapy by the U.S. Food
and Drug Administration, the majority of DEB patients still depend on palliative care,
an indication of the continued unmet therapeutic needs. In the past two decades,
*Corresponding authors: there has been a rapid advancement of gene therapy techniques, extensive research
Wenxin Wang
(wenxin.wang@ucd.ie) efforts, and pre-clinical studies focusing on the correction of DNA, RNA, and protein
Ming Li defects specific to DEB. In this review, we provide a comprehensive update on the
(mingli@fudan.edu.cn) current state of gene engineering strategies for DEB, including gene replacement,
Citation: Wang X, Ward J, pre-mRNA regulatory therapies, and gene editing techniques. In addition, this review
He W, Wang W, Li M. Advances critically evaluates the role and development of animal models in DEB research,
and challenges in gene therapy for
dystrophic epidermolysis bullosa: which are crucial for the progression of therapeutic strategies. Our discussion aims
Insights from therapeutic strategies to delineate the existing challenges and emphasize ongoing advancements in the
and animal models. Gene Protein Dis. gene therapy landscape for DEB, providing insights that may guide future research
2024;3(3):4047.
doi: 10.36922/gpd.4047 and clinical approaches.
Received: June 25, 2024
Accepted: August 13, 2024 Keywords: Epidermolysis bullosa; Dystrophic epidermolysis bullosa; Gene therapy;
Published Online: September 26, Animal models; COL7A1; Type VII collagen
2024
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution,
and reproduction in any medium, Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by skin
provided the original work is fragility. The latest international consensus meeting in 2020 defined EB as skin fragility
properly cited. resulting from blistering caused by minimal mechanical trauma, with disruption at the
1
Publisher’s Note: AccScience dermo-epidermal junction. EB is caused by mutations in the genes encoding important
Publishing remains neutral with proteins of the skin. Has et al. have summarized the general genotype-phenotype
2
regard to jurisdictional claims in 1
published maps and institutional correlations, although the EB phenotype is also strongly influenced by epigenetic
affiliations. and non-genetic modifying factors. EB has four main subtypes classified by the level

Volume 3 Issue 3 (2024) 1 doi: 10.36922/gpd.4047