Vesicular Glutamate Transporters in Astrocytes as Potential New Therapeutic Targets: Astrocyte-targeted Viral Vectors Expressing Inhibitory Nanobodies

Astrocytes, the main Central Nervous System (CNS) glial cell type, actively release transmitters, including glutamate, and thereby participate in physiological brain information processing. However, dysregulated transmitter from astrocytes can contribute to CNS disease pathogenesis progression. Therefore, targeting astrocyte glutamate is a promising new therapeutic strategy hyper-glutamatergic conditions, as it does not directly block glutamatergic neurotransmission. Basing on evidence that express Vesicular Glutamate Transporters (VGLUT), collaboration with other NCCR TransCure partners, we developed an innovative approach for astrocyte-selective delivery of nanobodies inhibiting VGLUT. We inserted anti-VGLUT nanobody constructs astrocyte-directed viral vectors were administered peripherally, crossed blood-brain-barrier led successful cell-specific CNS-wide expression nanobodies.