The role of gene therapy in neural injury repair

Neural injuries, including spinal cord injury, traumatic brain injury, and peripheral nerve injury, remain among the most challenging conditions in regenerative medicine due to the central nervous system's inherent limited capacity for self-repair. Traditional therapeutic approaches often struggle to effectively address the complex cellular and molecular barriers to neural regeneration. In recent years, gene therapy has rapidly emerged as a transformative strategy in neural repair, capable of precisely and persistently modulating the neuro-regenerative microenvironment. This review provides a comprehensive overview of recent advances in gene therapy for neural injury repair. We delve into fundamental genetic intervention strategies, including gene replacement, gene silencing, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-based gene editing technologies-alongside recent progress in both viral and non-viral vector delivery systems, such as adeno-associated virus capsid engineering and biomaterial-facilitated platforms. Mechanistically, gene therapy contributes to neural repair through multifaceted approaches: promoting axonal regeneration, inhibiting endogenous growth suppressors, enhancing neuroprotection, and modulating inflammatory responses and glial scar formation. Special emphasis is placed on circuit-specific targeting methods, spatially and temporally precise gene expression strategies, and combinatorial therapies that integrate gene delivery with biomaterials, stem cells, or physical stimuli. We further highlight preclinical in vivo findings across central and peripheral nerve injury models, as well as emerging insights from clinical trials in neurodegenerative disorders. Concurrently, this review critically evaluates key challenges currently faced, including immunogenicity, delivery specificity, and barriers to clinical translation. Finally, we will explore future directions in gene editing, RNA modulation, smart biomaterials, and multimodal therapeutic strategies, aiming to position gene therapy as a cornerstone of next-generation neuro-regenerative medicine.