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

Area of Science:

• Biotechnology
• Genetics
• Molecular Biology

Background:

• Collagen disorders are genetic conditions with unmet treatment needs, presenting diverse clinical features affecting multiple organ systems.
• Pathogenic variants in collagen genes lead to a wide spectrum of symptoms, from localized abnormalities to severe systemic complications.
• Current therapeutic strategies for collagen disorders are limited, necessitating innovative approaches.

Purpose of the Study:

• To review current gene-editing strategies for collagen-related diseases.
• To explore the application of Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas systems in treating conditions like osteogenesis imperfecta, Alport syndrome, and dystrophic epidermolysis bullosa.
• To highlight the potential and challenges of gene therapy in managing collagen disorders.

Main Methods:

• Overview of gene-editing technologies, including CRISPR-Cas9, base editing (BE), and prime editing (PE).
• Analysis of preclinical and clinical studies demonstrating the efficacy of gene therapy in enhancing collagen production and restoring tissue integrity.
• Examination of emerging strategies such as allele-specific inactivation.

Main Results:

• Gene editing, particularly CRISPR-Cas9, shows potential for targeted DNA modification to address collagen gene variants.
• Base editing and prime editing enable precise single-nucleotide alterations, offering safer therapeutic interventions.
• Preclinical and clinical data indicate that gene therapy can improve collagen production, tissue integrity, and symptom alleviation.

Conclusions:

• Gene editing technologies represent a transformative approach for treating collagen disorders, offering a potential one-for-all strategy.
• Despite challenges like delivery methods and off-target effects, advancements in gene editing promise more precise and safer genetic interventions.
• Gene editing is revolutionizing medicine by providing tailored therapeutic strategies for rare genetic disorders, including those affecting collagen.