Virus-mediated neuron-specific retrograde gene delivery in spinal cord injury

Abstract

To support neuronal function and restoration, virus-mediated neuron-specific retrograde transport is an effective tool for determining the localization of neuronal somas, identifying interneuronal connections, and facilitating the retrograde delivery of therapeutic transgenes. In experimental spinal cord injury, the retrograde transport of therapeutic transgenes offers several advantages over other more common delivery methods, such as targeted transfer of genetic constructs to specific types of spinal neuron somas, low invasiveness, relatively low risk of inflammatory response, and potential for repeated injections. Research on retrograde transport has extensively focused on enhancing its efficiency through capsid modification and application of novel promoters.

This review presents a detailed examination of the outcomes of virus-mediated neuron-specific retrograde transduction of transgenes after intramuscular injection of genetic constructs. In retrograde delivery technology, the ability to choose between monosynaptic and polysynaptic transports, depending on the specific viral vector used, was a positive aspect. The review also addresses the effects of virus-mediated retrograde transduction on both spinal motoneurons and interneurons, which collectively form motor neuronal networks. By delivering transgenes through retrograde transport along axons from the periphery to the perikarya of spinal neurons, not only localized effects within the spinal cord but also in supraspinal structures can be anticipated, a crucial aspect in restoring extensive neural connections.

Keywords

spinal cord injury / motoneuron / retrograde delivery / recombinant genes / viral vector

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