The Technology:
Severe neurodevelopmental encephalopathies caused by mutations in NMDA receptor (NMDAR) subunits currently lack disease-modifying therapies, with treatment limited to symptomatic management. A major barrier to gene therapy in this space has been the large size of GRIN genes, which approach or exceed the packaging limits of standard adeno-associated virus (AAV) vectors—preventing delivery of full-length, functional proteins.
This technology overcomes this limitation by enabling AAV-mediated delivery of full-length wild-type NMDA receptor subunits, including the largest GRIN genes, directly to neurons in the brain. By combining BBB-crossing AAV capsids with ultra-compact neuron-specific promoters and regulatory elements, the system achieves efficient neuronal expression while remaining within AAV packaging constraints.
The approach enables true gene replacement: reintroducing intact, functional NMDA receptor subunits to restore physiological receptor composition and synaptic signaling. Robust expression has been demonstrated in vitro and in vivo following systemic administration, with widespread neuronal transduction, correct synaptic localization, preserved receptor function, and no evidence of excitotoxicity.
Importantly, the strategy is applicable across multiple GRIN genes, positioning it as a scalable therapeutic solution for a broad class of GRIN-related encephalopathies, regardless of whether disease arises from haploinsufficiency or dominant-negative mutations.
Advantages:
• Full-length gene replacement for GRIN disorders, not partial or compensatory approaches.
• BBB-crossing AAV delivery, enabling minimally invasive systemic administration.
• Neuron-specific expression, reducing off-target risk and toxicity.
• Physiological receptor restoration, preserving normal synaptic regulation.
• Broad applicability across multiple GRIN genes and mutation types.
Applications and Opportunities:
• Gene therapy for GRIN-related encephalopathies, including epilepsy, neurodevelopmental delay, autism spectrum disorders, and cognitive impairment.
• First disease-modifying treatments for ultra-rare pediatric neurological diseases.
• Pipeline expansion to additional NMDA and glutamate receptor disorders.
• Platform extension to other large neuronal genes previously considered “undeliverable” by AAV.
Business Development Contacts
