Siglec transgenic mice and methods of use thereof

    公开(公告)号:US11147249B2

    公开(公告)日:2021-10-19

    申请号:US15836089

    申请日:2017-12-08

    Applicant: ALECTOR LLC

    Abstract: Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human Siglec immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human Siglec repertoire.

    Methods of screening for sortilin binding antagonists

    公开(公告)号:US10849992B1

    公开(公告)日:2020-12-01

    申请号:US15565063

    申请日:2016-04-07

    Applicant: ALECTOR LLC

    Abstract: The present disclosure provides methods of screening for a sortilin binding antagonist. In some embodiments, the methods include incubating an agent with a sortilin protein and a sortilin ligand, where the sortilin protein and sortilin ligand are each attached to a member of a fluorescence donor/acceptor pair, exciting the fluorescence donor of the fluorescence donor/acceptor pair, and detecting fluorescence emitted by the fluorescence donor at a second wavelength and fluorescence emitted by the fluorescence acceptor at a third wavelength. A decrease in the ratio of the fluorescence emitted by the fluorescence acceptor at the third wavelength to the fluorescence emitted by the fluorescence donor at the second wavelength, as compared to the ratio in the absence of the agent, indicates that the agent is a sortilin binding antagonist.

    Methods of screening for sortilin binding antagonists

    公开(公告)号:US12186409B2

    公开(公告)日:2025-01-07

    申请号:US17088237

    申请日:2020-11-03

    Applicant: Alector LLC

    Abstract: The present disclosure provides methods of screening for a sortilin binding antagonist. In some embodiments, the methods include incubating an agent with a sortilin protein and a sortilin ligand, where the sortilin protein and sortilin ligand are each attached to a member of a fluorescence donor/acceptor pair, exciting the fluorescence donor of the fluorescence donor/acceptor pair, and detecting fluorescence emitted by the fluorescence donor at a second wavelength and fluorescence emitted by the fluorescence acceptor at a third wavelength. A decrease in the ratio of the fluorescence emitted by the fluorescence acceptor at the third wavelength to the fluorescence emitted by the fluorescence donor at the second wavelength, as compared to the ratio in the absence of the agent, indicates that the agent is a sortilin binding antagonist.

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