Fine-tuning neuroinflammation through bidirectional modulation of 3′UTR length
This technology is a HuB-targeting therapeutic approach that modulates 3′ UTR length, altering immunostimulatory dsRNA levels and downstream interferon signaling to treat neuroinflammatory and neurodegenerative diseases.
Unmet Need: Mechanism-based strategy for treating RNA-triggered neuroinflammation
Neuroinflammatory and neurodegenerative diseases linked to disrupted RNA homeostasis, such as Aicardi-Goutières syndrome, lack effective, mechanism-based treatments that can safely reduce harmful, self-driven innate immune activation in neurons without undermining antiviral protection. Current care is largely supportive or relies on broad immunosuppression and anti-inflammatory strategies that do not correct the upstream source of aberrant immune triggering and can increase vulnerability to viral infection. This creates a need for more precise approaches to rebalance neuronal innate immune signaling, reducing pathological inflammation while preserving the necessary baseline antiviral immunity.
The Technology: A versatile method to modulate neuronal dsRNA-driven inflammation
This technology is a method for reducing neuroinflammation by delivering an effector that decreases the activity of the neuron-enriched RNA-binding proteins HuB and/or HuC. Lower HuB/HuC activity shifts neuronal RNA processing, including 3′ UTR regulation, to reduce the formation of endogenous immunostimulatory double-stranded RNA species that can inappropriately trigger innate immune sensors. As a result, downstream type I interferon signaling and associated inflammatory stress in neurons are dampened, helping treat neuroinflammatory or neurodegenerative pathology.
This technology has been validated in neurons derived from human embryonic stem cells and the HEK293T cell line.
Applications:
- Therapeutics for neuroinflammation after injury (stroke, TBI, spinal cord injury)
- Treatment of neurodegenerative diseases, including ALS, Alzheimer’s disease, and Huntington’s disease
- Research tool for studying neuroinflammatory pathways
- Research model for studying the pathogenic versus protective role of dsRNAs
- Treatment or prevention of viral infection
- Immunotherapy for cancer
- Platform for evaluating antisense/RNAi/gene therapy approaches targeting HuB/HuC
Advantages:
- Focused mechanism of action, rather than general anti-inflammatory approaches
- Dual-functionality, enabling both reduction or enhancement of dsRNA-driven responses
- Modulates neuronal immunity
- Adaptable to various disease contexts
Lead Inventor:
Patent Information:
Patent Pending(US19/400,788)
Related Publications:
Tech Ventures Reference:
IR CU23300, CU24306
Licensing Contact: Jerry Kokoshka