A spinal motor neuron-specific enhancer for cell-type specific gene expression control in the developing and adult central nervous system

A spinal motor neuron-specific enhancer for cell-type specific gene expression control in the developing and adult central nervous system

This technology is gene expression regulatory element that specifically targets cholinergic spinal motor neurons in the central nervous system and can be used for gene expression control throughout the mouse or human lifespan.

Unmet Need: Viral vector-compatible element for targeted gene expression control in cholinergic motor neurons beyond development

Currently the HB9 promoter is the standard tool for targeted gene expression control in cholinergic neurons. This promoter is large and therefore incompatible with viral vector packaging for delivery in vivo. Additionally, this promoter is only effective during embryonic development, limiting the window of effectiveness of the vector in postnatal and adult mice, which is a significant limitation in the study of neurodegenerative disease. Finally, off-target gene expression is a common and dangerous problem for existing gene therapy agents.

The Technology: Small, specific enhancer for cholinergic spinal motor neurons in early postnatal and adult mice

This technology is a gene enhancer, capable of facilitating either overexpression or knockdown of genes in a highly-specific and temporally-controlled manner in cholinergic motor neurons of the central nervous system. This enhancer is active in spinal motor neurons, but not in other spinal cholinergic or non-cholinergic cells, demonstrating its high cell type-specificity. This Chat enhancer is also compatible with adeno associated virus packaging for delivery, due to it’s comparably small size.

This technology has been validated in early postnatal and adult mice.

Applications:

• AAV deliverable gene therapy
• Gene therapy in cholinergic motor neurons with therapeutic applications in neurodegenerative disease
• Research tool for investigating cholinergic motor neuron activity, physiology, and pathology

Advantages:

• Smaller size, enabling AAV compatibility
• High specificity to cholinergic motor neurons
• AAV deliverable gene therapy
• Effective in young and adult mice
• Capable of inducing gene overexpression or knock down

Lead Inventor:

Hynek Wichterle, Ph.D.
Tulsi Patel, Ph.D.

Patent Information:

Patent Pending

Related Publications:

Tech Ventures Reference:

• IR CU22281, CU23033, CU23184

• Licensing Contact: Jerry Kokoshka