Department of Pathology, University of Cambridge, Cambridge, UK.
Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK.
J Neuroinflammation. 2024 Jul 28;21(1):183. doi: 10.1186/s12974-024-03156-x.
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.
创伤性脑损伤的治疗方法是全球尚未满足的医学需求。尽管神经重症监护方面的进展极大地提高了每年约 7000 万患者的存活率，但针对长期神经炎症过程和伴随的认知障碍（患者中很常见），几乎没有开发出治疗方法。这篇综述探讨了基因传递作为创伤性脑损伤的一种潜在治疗开发途径。我们讨论了基因传递通过在大脑内产生有益的生物制剂来发挥作用的能力。讨论了基因传递方式、有前途的载体和关键传递途径，以及生物有效载荷可以靶向的途径，以改善患者的长期预后。通过血脑屏障穿透和持续的局部产生相结合，基因传递有可能将具有有用生物学特性但药代动力学差的蛋白质转化为有效的治疗药物。最后，我们回顾了创伤性脑损伤的局限性和健康经济学，以及未来的基因传递方法是否对患者和医疗保健系统具有可行性。
