Gene editing for collagen disorders: current advances and future perspectives.

IF 4.5 3区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Klaudia Kocsy, Harry Wilkinson, Favour Felix-Ilemhenbhio, Benjamin Bax, Tom Van Agtmael, Mimoun Azzouz, Arshad Majid
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引用次数: 0

Abstract

Collagen disorders encompass a wide range of genetic conditions caused by pathogenic variants in collagen genes for which there is an unmet need for treatments. They present various clinical features, ranging from localised tissue abnormalities to severe systemic complications. Symptoms differ significantly and depend on the pathogenic variant, which can affect various systems, including the musculoskeletal, cardiovascular, and respiratory systems, highlighting the complex implications of collagen gene pathogenic variants and the wide range of expression patterns among different collagen types. Gene-editing technologies, particularly Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas systems, have emerged as promising therapeutic options for these disorders, representing a putative one-for-all treatment strategy. This review provides an overview of current gene-editing strategies aimed at collagen-related diseases, including osteogenesis imperfecta, Alport syndrome, and dystrophic epidermolysis bullosa. We explore the application of CRISPR-Cas9, which facilitates targeted DNA modifications, base editing (BE), and prime editing (PE), enabling precise single-nucleotide alterations without double-strand breaks (DSB). Preclinical and clinical studies have shown the potential of gene therapy to enhance collagen production, restore tissue integrity, and alleviate symptoms. However, challenges persist, including the lack of recurring mutations, the need for improved delivery methods, the reduction of off-target effects, and the development of novel therapies. Despite these challenges, advancements in gene editing techniques appear promising in enhancing editing efficiency while minimising unintended mutations, paving the way for more precise and safer genetic interventions for collagen disorders. Gene editing is fundamentally transforming medicine and biotechnology. Its applications encompass advanced diagnostics, tailored therapeutic strategies, and solutions for rare genetic disorders. By enabling precise genetic modifications, gene editing is paving the way for treatments of previously untreatable diseases, including those linked to collagen pathogenic variants. This review discusses the latest advancements in gene therapy techniques targeting collagen-related disorders. It explores innovative approaches like CRISPR-Cas9-mediated gene editing and highlights emerging strategies, such as allele-specific inactivation and base editing (BE). By examining these cutting-edge therapies and their potential clinical applications, this review highlights the transformative impact of gene editing in treating collagen-related conditions, while also identifying critical challenges and future directions for research.

胶原蛋白疾病的基因编辑:当前进展和未来展望。
胶原蛋白疾病包括由胶原蛋白基因的致病性变异引起的广泛的遗传疾病,对这些疾病的治疗需求尚未得到满足。它们表现出各种临床特征,从局部组织异常到严重的全身并发症。症状差异显著,取决于致病变异,可影响多种系统,包括肌肉骨骼、心血管和呼吸系统,这突出了胶原基因致病变异的复杂含义和不同胶原类型之间广泛的表达模式。基因编辑技术,特别是聚集规律间隔回文重复序列(CRISPR)-Cas系统,已经成为这些疾病的有希望的治疗选择,代表了一种假定的“一刀切”的治疗策略。本文综述了目前针对胶原蛋白相关疾病的基因编辑策略,包括成骨不全症、Alport综合征和营养不良大疱性表皮松解症。我们探索了CRISPR-Cas9的应用,它促进了靶向DNA修饰、碱基编辑(BE)和引物编辑(PE),实现了精确的单核苷酸改变,而不需要双链断裂(DSB)。临床前和临床研究表明,基因治疗在增强胶原蛋白生成、恢复组织完整性和缓解症状方面具有潜力。然而,挑战仍然存在,包括缺乏重复突变,需要改进给药方法,减少脱靶效应,以及开发新的治疗方法。尽管存在这些挑战,基因编辑技术的进步似乎有望提高编辑效率,同时最大限度地减少意外突变,为更精确、更安全的胶原蛋白紊乱基因干预铺平道路。基因编辑正在从根本上改变医学和生物技术。它的应用包括先进的诊断、量身定制的治疗策略和罕见遗传疾病的解决方案。通过实现精确的基因修饰,基因编辑为治疗以前无法治愈的疾病铺平了道路,包括那些与胶原致病变异有关的疾病。本文综述了针对胶原蛋白相关疾病的基因治疗技术的最新进展。它探索了创新方法,如crispr - cas9介导的基因编辑,并强调了新兴策略,如等位基因特异性失活和碱基编辑(BE)。通过研究这些前沿疗法及其潜在的临床应用,本综述强调了基因编辑在治疗胶原蛋白相关疾病方面的变革性影响,同时也确定了关键的挑战和未来的研究方向。
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来源期刊
Gene Therapy
Gene Therapy 医学-生化与分子生物学
CiteScore
9.70
自引率
2.00%
发文量
67
审稿时长
4-8 weeks
期刊介绍: Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.
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