Humanized NOTCH receptor with hinge domain

The humanized HingeNotch receptor addresses immunogenicity and size constraints of first-generation SynNotch receptors by enabling compact design and efficient ligand-dependent gene regulation, enhancing clinical suitability.

JP7863331B2Active Publication Date: 2026-05-21RGT UNIV OF CALIFORNIA
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
RGT UNIV OF CALIFORNIA
Filing Date
2021-04-08
Publication Date
2026-05-21

AI Technical Summary

Technical Problem

First-generation SynNotch receptors face challenges such as immunogenicity due to non-human sequences and size constraints, limiting their clinical application and efficiency.

Method used

Development of a novel humanized Notch receptor, HingeNotch, which lacks the Notch extracellular subunit and incorporates an extracellular oligomerization domain, enabling compact size and efficient ligand-dependent gene regulation, facilitating clinical use and inclusion of additional components.

Benefits of technology

The HingeNotch receptor provides effective, spatial and temporal control of gene expression and cellular activity, reducing immunogenicity and size limitations, making it suitable for clinical applications.

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Patent Text Reader

Abstract

The present disclosure generally relates to, inter alia, a new class of chimeric Notch receptors engineered to contain fully humanized transcriptional effectors and regulate gene expression and cellular activity in a ligand-dependent manner. These novel chimeric Notch receptors surprisingly retain the ability to transduce signals in response to ligand binding, despite the complete lack of the Notch extracellular subunit (NEC), including the negative regulatory region (NRR), previously thought to be essential for Notch receptor function. Furthermore, the novel receptors described herein incorporate an extracellular oligomerization domain to promote oligomerization of the chimeric receptor. Compositions and methods useful for producing such receptors, nucleic acids encoding the receptors, engineered cells genetically modified with the nucleic acids, and the like, as well as methods for modulating cellular activity and / or treating various diseases, such as cancer, are also provided.
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