Chloride transporter ClC-7 and cell-based screening method

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This patent discloses genetically modified versions of the CIC-7 (ClC-7) protein, a chloride/proton transporter normally located inside cells, that are engineered to be expressed on the cell surface or plasma membrane by disrupting certain recognition motifs necessary for endosomal/lysosomal targeting. This breakthrough allows CIC-7 to become directly accessible to test compounds in cell-based assays. The resulting system enables efficient, high-throughput screening of drugs or compounds that modulate CIC-7 activity, facilitating the identification of new treatments for diseases such as osteoporosis.

Use CasesContent extracted from patent full text and abstract with AI.

• High-throughput screening of small molecules, peptides, or other therapeutic compounds for ability to inhibit or modulate CIC-7 activity.
• Drug discovery for osteoporosis by finding compounds that block or alter ClC-7 function in osteoclasts to reduce bone resorption.
• Research into CIC-7 and its role in bone mineralization and other lysosomal or osteoclast-related diseases.
• Diagnostic tests or kits to identify modulators of chloride/proton transport relevant for rare bone diseases or genetic disorders associated with CIC-7 mutation.
• Functional characterization and electrophysiological studies of CIC-7 in a more accessible cellular location, aiding basic research.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides a practical cell-based assay for drug screening that overcomes the inaccessibility of native CIC-7 inside lysosomes/endosomes, enabling real high-throughput testing.
• Accelerates drug discovery for osteoporosis and potentially other bone-weakening disorders by targeting a validated molecular mechanism.
• Allows direct measurement of chloride and/or proton transport affected by candidate drugs, leading to more precise and relevant results.
• Facilitates research into the fundamental biology and pathophysiology of CIC-7, Ostm1, and their interactions.
• The mutations and techniques can be adapted for other cell types or for producing recombinant CIC-7 for further study, broadening scientific and biomedical applications.

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Inventors & Applicants

Patent Abstract

The invention relates to a CIC-7 protein that is presented on the cell surface and/or plasma membrane, characterised in that the interaction between CIC-7 and the endosomal and/or lysosomal sorting machinery, such as one or more adaptor proteins (AP) and/or Golgi-localized, ³-ear containing, Arf-binding adaptor proteins (GGA), is inhibited and/or disrupted, preferably by mutation or deletion of the amino acid sequences of one or more AP and/or GGA recognition motifs. The invention further relates to a cell-based assay system in which a CIC-7 protein is presented on the cell surface and/or plasma membrane of a cell, with which test compounds are screened for activity in modulating proton and/or chloride transport via CIC-7. Such compounds are intended for application in the treatment of osteoporosis.