Biomaterial-Based Gene Delivery to Central Nervous System Cells for the Treatment of Spinal Cord Injury

Spinal cord injury (SCI) is a devastating traumatic injury often causing permanent loss of function. The challenge of treating SCI stems from the development of a complex pathophysiology at the site of injury, involving multiple biochemical cascades, widespread inflammation, blood supply interruption, inhibitory scar formation, and poor regrowth of injured axons. Clinical options are limited to surgical stabilization and attempt to ameliorate secondary damage following injury. Gene therapy has significant potential to tackle multiple aspects of SCI and improve functional outcomes. The emergence of a diverse array of biomaterial-based nonviral nanoparticle vectors capable of delivering gene-modifying nucleic acids offers the potential to improve the efficiency and specificity of genetic cargos for spinal cord regeneration. In this review, the progress that has been made in the field of SCI repair and the different types of nanoparticles and nucleic acid cargoes that have been used are outlined, placing a particular focus on the different cell types and pathways targeted. While many challenges remain, a perspective on the future of the field of nanoparticle-mediated gene delivery for SCI is provided, including using biomaterial scaffolds engineered specifically for SCI to deliver gene therapeutics and the exciting opportunities that exist in the post-COVID landscape. Spinal cord injury is a catastrophic injury that leads to long-term disability. This review discusses nonviral gene therapy approaches that have been employed to promote repair after injury. Through the targeting of different cells and pathways, this state-of-the-art strategy can revolutionize treatment by simultaneously promoting survival and axon regrowth attenuating scarring, and reducing inflammation, ultimately restoring function to the patient.image & COPY; 2023 WILEY-VCH GmbH

Automated summary

Spinal cord injury is a devastating traumatic injury that often results in permanent loss of function. Gene therapy using nonviral nanoparticle vectors has the potential to improve spinal cord regeneration by targeting multiple aspects of the injury and enhancing specificity. Despite challenges, nanoparticle-mediated gene delivery holds great promise for the future of spinal cord injury treatment.