Traceless linker and methods of use thereof
The para-nitro carbonate-disulfide-PEG-trans-cyclooctene linker facilitates efficient conjugation and rapid release of bioactive molecules under reducing conditions, addressing the need for effective delivery of genome editing enzymes.
WO2025128586A1 Publication Date: 2025-06-19RGT UNIV OF CALIFORNIA
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Patent Information
- Application Number
- PCT/US2024/059402
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-11
- Filing Date
- 2024-12-10
- Publication Date
- 2025-06-19
AI Technical Summary
Technical Problem
There is a need for efficient reduction-sensitive linkers that can rapidly release bioactive molecules from therapeutically useful cargoes, such as genome editing enzymes, under physiological reducing conditions.
Method used
A para-nitro carbonate (PNC)-disulfide (DS)-PEG-trans-cyclooctene (TCO) linker is used to reversibly tether proteins like Cas9, allowing for efficient conjugation of functional groups and rapid release under reducing conditions.
Benefits of technology
The linker enables rapid and efficient conjugation and release of bioactive molecules, improving delivery and targeting of molecules like CRISPR-Cas effector proteins to cells.
✦ Generated by Eureka AI based on patent content.
Abstract
The present disclosure provides reversible / traceless linkers that include functional groups for attaching a first and second molecule of interest, where the linker includes a reduction sensitive disulfide linker that undergoes cleavage under physiological reducing conditions, releasing the first molecule of interest. The release is fully reversible in that the first molecule is restored to its "pre-linker" state. The present disclosure provides compounds comprising a first and a second molecule of interest linked by a linker of the present disclosure. The present disclosure provides methods of using a compound of the present disclosure to deliver a molecule of interest. The present disclosure provides methods of modifying a target nucleic acid in a cell, which use a reversible / traceless linker to deliver a gene editing protein.
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