Method for inducing aneuploidy and / or chromosomal instability in human or non-human primate pluripotent stem cells and diagnostic / therapeutic uses thereof

A novel method induces aneuploidy and chromosomal instability in hPSCs by treating them with chromosome missegregation-inducing compounds, effectively addressing the limitations of current methods and enabling the identification of genes and pathways affected by aneuploidy and the development of therapeutic agents targeting aneuploid cells.

WO2025101836A1 Publication Date: 2025-05-15TRUSTEES OF DARTMOUTH COLLEGE THE
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Patent Information

Application Number
PCT/US2024/055039
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-05-03
Filing Date
2024-11-08
Publication Date
2025-05-15

AI Technical Summary

Technical Problem

Current methods for inducing aneuploidy and chromosomal instability in human pluripotent stem cells (hPSCs) are limited, and there is a need for effective methods to identify genes and pathways affected by different ploidy states and chromosomal stability, as well as to develop therapeutic agents that selectively act on cells with varying ploidy states or chromosomal stability.

Method used

A novel method is developed to induce aneuploidy and chromosomal instability in hPSCs by treating euploid cells with compounds that cause chromosome missegregation, such as microtubule inhibitors, resulting in a mixed cell population with a high percentage of aneuploid cells. This method allows for the creation of a durable aneuploid phenotype in hPSCs that maintains normal characteristics, including pluripotency and cell cycle regulation.

Benefits of technology

The method effectively induces a durable aneuploid state in hPSCs, allowing for the identification of genes and pathways affected by aneuploidy and chromosomal instability, as well as the development of therapeutic agents that selectively target aneuploid cells. The aneuploid hPSCs retain normal characteristics, such as pluripotency and cell cycle regulation, making them suitable for therapeutic and research applications.

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Abstract

The invention provides a novel screening platform and aneuploidal pluripotent stem cells and compositions containing for use in the identification of genes / pathways affected by different ploidy states or chromosomal stability and therapeutic agents that selectively act on cells of different ploidy states or chromosomal stability. In particular the present invention provides novel methods for inducing aneuploidy and / or chromosomal instability in human pluripotent stem cells (hPSCs) or non-human pluripotent stem cells (nhpPSCs). The present application also relates to the use of such methods and aneuploid hPSCs or nhpPSCs obtained thereby for identifying genes which are affected by different ploidy states and / or chromosomal stability and for identifying therapeutic agents that selectively or preferentially act on cells of different ploidy states and / or which affect chromosomal stability.
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