Products and methods for treatment

By inhibiting ubiquitination during the maturation of erythroid cells, the method maintains high concentrations of therapeutic proteins in red blood cells, addressing bioavailability and immune compatibility issues, enhancing therapeutic efficacy.

JP2026086602APending Publication Date: 2026-05-26UNIV OF BRISTOL
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Patent Information

Authority / Receiving Office
JP Β· JP
Patent Type
Applications
Current Assignee / Owner
UNIV OF BRISTOL
Filing Date
2026-02-06
Publication Date
2026-05-26

AI Technical Summary

Technical Problem

Existing methods for administering proteins or polypeptides, such as enzyme replacement therapy, face challenges in ensuring bioavailability and immune system compatibility while maintaining the integrity and lifespan of red blood cells, particularly due to issues with hypotonic hemolysis and genetic engineering techniques.

Method used

A method is developed to maintain target proteins or polypeptides in reticulocytes and erythrocytes by inhibiting ubiquitination during cell maturation, using genetic manipulation to prevent ubiquitin-mediated degradation, allowing for high concentrations of therapeutic proteins in enucleated red blood cells.

Benefits of technology

This approach enhances the retention and abundance of therapeutic proteins in red blood cells, reducing the need for frequent transfusions and minimizing immune response, thereby improving therapeutic efficacy.

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Abstract

The present invention provides a method for producing reticulocytes containing increased levels of target protein or polypeptide. [Solution] The method comprises (a) preparing a erythrocyte precursor capable of expressing the target protein or polypeptide, (b) expressing the target protein or polypeptide, and (c) maturing the erythrocyte precursor into a reticulocyte, wherein the target protein or polypeptide is configured and / or inhibited so as to interfere with or prevent ubiquitination of the target protein or polypeptide when the erythrocyte precursor is matured into a reticulocyte. Erythrocytes, pharmaceutical compositions and related methods of use, as well as a method for screening proteins or polypeptides that are degraded by ubiquitination during the maturation of erythrocyte precursors, are also provided.
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