The following review from Gene Therapy of Nature presents the advances and future prospects of gene editing in relation to collagen disorders.
Collagen disorders include a broad spectrum of inherited conditions caused by harmful mutations in collagen-related genes, many of which currently lack effective treatments. These disorders can lead to a wide variety of symptoms, ranging from localized tissue problems to serious systemic complications. The clinical presentation varies greatly depending on the specific mutation involved, which may impact systems such as the musculoskeletal, cardiovascular, and respiratory systems. This variability reflects the complex effects of collagen gene mutations and the diverse roles different collagen types play in the body.
Gene-editing technologies—especially CRISPR-Cas systems—are showing significant promise as potential therapies for these conditions, offering a possible unified approach to treatment. This review summarizes current gene-editing strategies under investigation for collagen-related diseases such as osteogenesis imperfecta, Alport syndrome, and dystrophic epidermolysis bullosa. It examines the use of CRISPR-Cas9 for targeted DNA changes, as well as newer techniques like base editing (BE) and prime editing (PE), which allow for precise single-nucleotide edits without causing double-strand DNA breaks.
Both preclinical and clinical studies suggest that gene therapy may enhance collagen synthesis, improve tissue function, and reduce disease symptoms. However, several challenges remain, including the wide variety of mutations involved, limitations in delivery systems, potential off-target effects, and the ongoing need for innovative treatment approaches.
Despite these obstacles, progress in gene-editing tools is driving improvements in editing precision and safety, laying the foundation for more effective genetic treatments for collagen disorders. Gene editing is rapidly reshaping medicine and biotechnology, offering new possibilities for accurate diagnosis, personalized therapies, and solutions for rare genetic diseases. By enabling targeted genetic changes, gene editing opens the door to treatments for previously untreatable conditions, including those caused by mutations in collagen genes. This review highlights recent breakthroughs in gene therapy for collagen-related disorders, including novel methods such as allele-specific inactivation and base editing, and emphasizes the future potential of these technologies, while also outlining ongoing challenges and research needs.