Viral Method to Express Regenerative Proteins in Spinal Cord Injured Axons

Background & Unmet Need

• Spinal cord injury and other traumatic axonal injuries currently have limited treatment options
• Goal of therapy: promote axonal growth and regeneration, to improve motor and sensory function in patients
• Gene therapies that increase the expression of axonal regeneration-promoting proteins is a potential treatment strategy, but is limited by the unique morphology of the affected neurons
• Unmet Need: Method that enables delivery of gene therapy and expression of regenerative proteins directly to injured axons, without requiring administration at cell bodies in the brain

Technology Overview

• The Technology: Method for targeted gene expression in axons using expression of regenerative proteins from an alphavirus vector
• The Discovery: Protein translation occurs in the axons of neuronal cells when axonal ribosomes are presented with an RNA including an internal ribosome entry site (IRES)
• RNA alphaviruses successfully enter axons and induce the express of genes linked to an IRES
• Technology may be used to express a variety of regenerative proteins, such as dominant-negative variants of RhoA or RhoA-activated kinase, adenylyl cyclase, src kinase, and cyclic AMP-response element-binding protein (CREB)

Technology Applications

• Treatment of spinal cord injuries
• Treatment of axonopathies such as Charco-Marie-Tooth disease and diabetic neuropathy
• Promoting axonal growth and regeneration

Technology Advantages

• Targeted axonal expression of regenerative proteins
• Modular alphavirus expression system