Methods for modulating RNA processing

NEAR constructs address the limitations of CRISPR systems by precisely modulating RNA processing events, enhancing safety and efficacy in identifying and analyzing RNA targets for conditions like neurodegenerative diseases and cancers.

WO2025166110A1 Publication Date: 2025-08-07RGT UNIV OF CALIFORNIA
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Patent Information

Application Number
PCT/US2025/013954
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-02-02
Filing Date
2025-01-31
Publication Date
2025-08-07

AI Technical Summary

Technical Problem

Current methods for targeting RNA processing events, such as CRISPR systems, pose risks of altering DNA sequences, have PAM requirements, and can trigger immunogenic responses, limiting their effectiveness and safety in modulating RNA processing.

Method used

Utilization of nuclear expressed antisense RNA (NEAR) constructs to modulate RNA processing events by recruiting mammalian nuclear ribonucleoproteins, allowing precise targeting and analysis of RNA processing targets in cells.

Benefits of technology

NEAR constructs enable efficient and specific modulation of RNA processing events, such as alternative splicing and polyadenylation, with reduced off-target effects and immunogenicity, facilitating the identification and analysis of RNA processing targets associated with conditions like neurodegenerative diseases and cancers.

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Abstract

Provided herein are methods and materials for performing pooled screening, modulating RNA processing events, and / or analyzing a sample to identify an RNA processing event or RNA processing target associated with a condition. For example, an RNA processing event can be alternative splicing, constitutive splicing, polyadenylation, methylation, folding, degradation, pseudouridylation, and / or adenosine to inosine RNA editing. In some embodiments, the method includes selecting for a phenotype of interest.
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