Chimeric system for functionally expressing and screening catsper channel

WO2026128336A3PCT designated stage Publication Date: 2026-07-23YALE UNIVERSITY
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Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
YALE UNIVERSITY
Filing Date
2025-12-08
Publication Date
2026-07-23

AI Technical Summary

Technical Problem

Existing technologies face challenges in expressing and screening CatSper channels in mammalian cells due to ER/Golgi retention, limiting direct drug screening and hindering the development of male contraceptives and infertility treatments targeting sperm motility.

Method used

Engineering chimeric CatSper channels by replacing the cytoplasmic domains with those from diatom-encoded single-domain voltage-gated channels, enabling the channels to traffic to the plasma membrane and form functional calcium channels in mammalian cells, suitable for high-throughput screening.

Benefits of technology

Facilitates direct and robust drug screening for modulators of CatSper channels, potentially leading to effective male contraceptives and infertility treatments by enhancing sperm motility and fertility.

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Abstract

The present invention is directed to chimeric CatSper channel proteins which are engineered by replacing the cytoplasmic domain of CatSper with those from a related channel with proven surface localization. The novel chimeric channels with the intact CatSper pore successfully traffic to the surface of mammalian cells and conduct calcium. The invention therefore is directed to chimeric CatSper channel proteins, nucleotide sequences which encode for such channel proteins, expression vectors which express such proteins and mammalian cells in which CatSper channel proteins have localized onto cell surfaces as well as methods for recording calcium flux in cells which comprise chimeric CatSper channel proteins localized on the cell surface. The present invention can be used to identify ligands and molecules which exhibit inhibition of fertility (contraception) or enhanced fertility (fertility agents).
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