The use of viral vectors to promote repair after spinal cord injury

Spinal cord injury (SCI) is a devastating event that can permanently disrupt multiple modalities. Unfortunately, the combination of the inhibitory environment at a central nervous system (CNS) injury site and the diminished intrinsic capacity of adult axons for growth results in the failure for robust axonal regeneration, limiting the ability for repair. Delivering genetic material that can either positively or negatively modulate gene expression has the potential to counter the obstacles that hinder axon growth within the spinal cord after injury. A popular gene therapy method is to deliver the genetic material using viral vectors. In this review, we will discuss some of the aspects to consider when utilizing a viral vector approach to as a therapy for SCI. Additionally, we will discuss some recent applications of gene therapy to target extrinsic and/or intrinsic barriers to promote axon regeneration after SCI in preclinical models.

• 1
  Adeno-associated virus (AAV) is a common vector of choice for gene therapy. Its low immunogenicity and risk of insertional mutagenesis combined with the ability to transduce both, dividing and non-dividing cells, make it an attractive option for researchers
• 2
  Selecting the correct promoter is a crucial factor to achieve cell-specific viral transduction and efficient gene expression. While some promoters allow strong gene expression in many cell types in the CNS, others are cell type specific and limit what types of cells to express the transgene
• 3
  Gene therapy can be used to tackle the various hindrances to neural repair after SCI, including removing inhibitory molecules to produce a more favorable environment, including by providing trophic support, while targeting neuro-intrinsic mechanisms to promote axon regeneration, and inducing axon remyelination.