Integrating CRISPR technology into neurotrauma research: opportunities and challenges in addressing synaptic dysfunction after TBI

Traumatic brain injury (TBI) is a major global cause of neurological disability, with long-term consequences that include synaptic dysfunction and rare synaptopathies. The CRISPR/Cas9 gene-editing system has emerged as a powerful tool in neurotrauma research due to its efficiency in gene knockout, knock-in, transcriptional regulation, and base editing. Recent studies demonstrate its potential in modulating synaptic proteins such as PSD-95, Synaptophysin, GluN1, and GluA2, providing insight into mechanisms of TBI-related synaptopathies. While CRISPR offers remarkable opportunities to advance our understanding and treatment of neurotrauma, challenges remain, including off-target effects, error-prone repair, inefficient delivery systems, and immunogenicity. Overcoming these barriers through improved epigenetic tools, targeted non-viral delivery methods, and multiplexed modulation strategies may enable more precise interventions. Ethical oversight and long-term safety monitoring will be critical to harness CRISPR's full therapeutic potential for addressing TBI-associated synaptic dysfunction.