Modulating inflammation by altering 3’ Untranslated Region (3’ UTR) length

This technology describes a method for immunomodulation via alteration of the length of 3’ Untranslated Regions (3’ UTRs) to control inflammation, which may be relevant in developing immunotherapies or neuroinflammatory therapies.

Unmet Need: Method for immunomodulation and fine-tuning inflammation

Loss of RNA homeostasis is known to contribute to various neurodegenerative and neuroinflammatory diseases, but the molecular mechanisms promoting these inflammatory pathways are unclear. Viral double-stranded RNAs (dsRNAs) are known to promote innate immune responses, but the mechanisms underlying these processes and how they may be targeted therapeutically have not been extensively explored. Studying the pathways through which dsRNAs can trigger neuroinflammation can identify therapeutic targets for neuroinflammatory diseases, as well as cancer immunotherapies. Assessing the protective versus pathogenic role of dsRNAs and their association with 3’UTR lengths can be useful to better understand neuron-specific toxic inflammation.

The Technology: Method for immunomodulation to reduce pathological neuroinflammation

This technology identifies molecular mechanisms that can alter double-stranded (dsRNA) levels in different cell types to target toxic inflammation and the loss of RNA homeostasis. This technology distinguishes the association between mRNAs with elongated 3’ Untranslated Regions (3’ UTRs) and immunogenic dsRNAs. Fine-tuning 3’ UTR length and specifically inducing 3’ UTR lengthening can be used to promote an immune response, indicating mechanisms to boost or suppress immune responses and inflammation. Immunomodulation via the modification of the length of 3’ UTRs can be used to develop therapies for neurodegenerative and neuroinflammatory diseases as well as cancer immunotherapies.

This technology has been validated with human stem cell lines.

Applications:

• Immunotherapy for cancer and neuroinflammatory and neurogenerative diseases
• Research model to study inflammatory pathways
• Platform to study pathogenic versus protective role of dsRNAs and dsRNA homeostasis
• Approach to suppress or boost inflammation
• Platform to study the functionality of long 3’ UTRs

Advantages:

• Compatible with study of molecular mechanisms in different cell types
• Enables assessment of neuron-specific toxic inflammation
• Facilitates fine-tuning and modulation of immune response
• Enables the study of RNA stability

Lead Inventor:

Hachung Chung, Ph.D.

Patent Information:

Patent Pending (WO/2024/249458)

Related Publications:

• Dorrity TJ, Shin H, Wiegand KA, Aruda J, Closser M, Jung E, Gertie JA, Leone A, Polfer R, Culbertson B, Yu L, Wu C, Ito T, Huang Y, Steckelberg AL, Wichterle H, Chung H. “Long 3'UTRs predispose neurons to inflammation by promoting immunostimulatory double-stranded RNA formation.” Sci Immunol. 2023 Oct 27; 8(88):eadg2979

Tech Ventures Reference:

• IR CU23300

• Licensing Contact: Jerry Kokoshka