Author by : Tasneem Hassan Muna
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Description : Spinal cord injury (SCI) affects millions of people worldwide. It is a complicated disease with no cure that leaves patients with permanent neurological deficits, mainly because damaged neurons fail to regenerate after SCI. Schwann cells (SC) play important role in supporting axon regeneration after peripheral nerve injury. Their regenerative potential makes them ideal candidates for use in SCI to support axon regeneration. However, a significant improvement in recovery is seen only when SC are combined with additional therapeutic agents. Administration of such agents often requires multiple injections, which increases chances of inflammation, infection and complicates dosage control. Engineered SC that produce therapeutic agents at the site of SCI can obviate the need for multiple injections. What is currently lacking is an approach that allows to control engineered SC post-transplantation. The objective of this project was to test an optogenetic approach to controlling gene expression in SC. Light in the near-infrared window (NIRW) encompasses the spectrum of 670 to 900 nm. NIRW light penetrates deeply through mammalian tissues and is safe for medical applications. NIRW light represents a non-invasive way of achieving spatio-temporal control over transplanted cells. In this study, we engineered SC stably expressing a NIRW light-responsive adenylyl cyclase, IlaM5. We showed that NIRW irradiation activates expression of a reporter luciferase from a cAMP-dependent promoter. Several fold increase in luciferase levels were observed following a one-hour long irradiation of SC. The activation levels were higher if biliverdin, the chromophore for IlaM5, was added to SC exogenously. This study represents a proof-of-concept that SC can be effectively engineered to respond to NIRW light, which opens opportunities for translational applications of engineered, NIRW light-controlled SC in spinal cord regeneration.