Methods and Agents for Increasing Rbm3 Expression

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention describes methods and agents, including antisense oligonucleotides (ASOs) and CRISPR/Cas-based genome editing systems, that can increase the expression of the RNA-binding motif protein 3 (RBM3) by preventing the inclusion of a specific 'poison' exon (exon 3a) in the RBM3 mRNA. Normally, inclusion of exon 3a leads to nonsense-mediated decay (NMD) of RBM3 mRNA, reducing RBM3 protein levels. By targeting this exon or its splice sites with ASOs or base editing tools, RBM3 expression can be upregulated without the need for hypothermia, potentially providing neuroprotection and treating a range of neurological or neurodegenerative conditions.

Use CasesContent extracted from patent full text and abstract with AI.

• Therapeutic upregulation of RBM3 expression in neurons to provide neuroprotection during or after events like stroke, traumatic brain injury, or cardiac surgery.
• Treatment or prevention of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, prion diseases, frontotemporal dementia, tauopathies, and ALS.
• Adjunct therapy to mitigate neurological damage due to hypoxic-ischemic encephalopathy in newborns or after anoxic/ischemic events in adults.
• Potential treatment of certain psychiatric conditions (e.g., depression or anxiety) where RBM3 may play a role.
• Avoidance of therapeutic hypothermia (cooling) in neuroprotection, reducing associated risks and simplifying clinical interventions.
• Cancer therapy applications—potentially improving prognosis where high RBM3 expression correlates with improved survival in specific cancers (e.g., gastric, breast, colon cancer).

BenefitsContent extracted from patent full text and abstract with AI.

• Enables controlled upregulation of RBM3 without the need for risky and complex therapeutic hypothermia procedures, thus avoiding complications like blood clots or pneumonia associated with cooling.
• Provides a novel, targeted molecular approach (ASOs or genome editing) for increasing an endogenous neuroprotective protein in the brain.
• Applicable to a broad range of acute (e.g., stroke, brain injury) and chronic (e.g., Alzheimer’s, ALS) neurological diseases.
• Long-lasting, robust neuroprotection demonstrated in animal models, including in vivo increase of RBM3 and preservation of neuronal health.
• Uses modalities (ASOs, gene editing) with increasing regulatory acceptance and clinical translation (e.g., similar to approved drugs like nusinersen for spinal muscular atrophy).
• Potential for combination approaches (e.g., ASO plus CRISPR/base editing), dose titration, and custom delivery routes (e.g., intrathecal, systemic, oral, or inhaled formulations).
• Possibility to expand use for cancer prognosis or therapy, beyond neurodegeneration.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The invention provides agents (e.g., antisense oligonucleotides (ASOs), a CRISPR/Cas-based base editing system) capable of increasing expression of RNA-binding motif protein 3 (RBM3) by targeting a poison exon of RBM3, exon 3a, or a splice site thereof. Also disclosed are methods for increasing expression of RBM3 in a cell, methods of treating or preventing a disease affected by RMB3 expression in a subject, or methods for providing neuroprotective treatment to a subject.