Therapeutics for traumatic brains injuries constitute a global unmet medical need. Despite the advances in neurocritical care, which have dramatically improved the survival rate for the ~ 70 million patients annually, few treatments have been developed to counter the long-term neuroinflammatory processes and accompanying cognitive impairments, frequent among patients. This review looks at gene delivery as a potential therapeutic development avenue for traumatic brain injury. We discuss the capacity of gene delivery to function in traumatic brain injury, by producing beneficial biologics within the brain. Gene delivery modalities, promising vectors and key delivery routes are discussed, along with the pathways that biological cargos could target to improve long-term outcomes for patients. Coupling blood-brain barrier crossing with sustained local production, gene delivery has the potential to convert proteins with useful biological properties, but poor pharmacodynamics, into effective therapeutics. Finally, we review the limitations and health economics of traumatic brain injury, and whether future gene delivery approaches will be viable for patients and health care systems.© 2024. The Author(s).
