DESIGN OF SYNTHETIC miRNAS TO RESTORE THE CORRECT GENE DOSAGE OF GENES ASSOCIATED WITH T LYMPHOCYTE EXHAUSTION
WO2025238594A3 Publication Date: 2026-01-02FOND INST ITAL DI TECH
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Patent Information
- Application Number
- PCT/IB2025/055088
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-05-16
- Filing Date
- 2025-05-15
- Publication Date
- 2026-01-02
AI Technical Summary
Technical Problem
Existing methods to address T cell exhaustion, such as CRISPR-mediated knockout, result in permanent deletion of essential genes, leading to increased off-target responses and cytotoxicity, and fail to provide precise control over gene expression.
Method used
Development of synthetic microRNAs (miRNAs) targeting the TOX gene, engineered with a 5’-UTR, antisense TOX gene sequence, loop, and complementary sequence, controlled by polymerase II promoters for inducible regulation, to downregulate TOX expression.
Benefits of technology
The synthetic miRNAs effectively downregulate TOX, restoring T cell functionality and reducing immune checkpoint receptor expression, enhancing T cell cytotoxicity and cytokine production, thus improving T cell therapy efficacy.
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Abstract
The invention concerns synthetic miRNAs targeting the TOX gene and uses thereof. Pharmaceutical compositions comprising such miRNAs and uses thereof in the medical field, in particular in the treatment of cancer diseases and immunotherapy, are also described.
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