ArticleScience advances2024
Uncovering receptor-ligand interactions using a high-avidity CRISPR activation screening platform.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Rapid discovery of cell-surface glycosylation regulators using a lectin-based magnetic CRISPR screen.Cell reports methods · 2026Article
- Exercise-induced myokines in metabolic regulation: mechanisms, mimetics, and translational potential.Archives of pharmacal research · 2026Review
- CRISPR activation screens map the genomic landscape of cancer glycome remodeling.Cell genomics · 2026Article
- Approaches to deorphanize secretome: Classical, computational, and next generation strategies to reveal ligand-receptor networks.EXO : beyond the cell · 2026Article
- Multiplexed Pan Soluble Ligandome Assaying via OASIS.bioRxiv : the preprint server for biology · 2025Article
- Identification of host factors for livestock and poultry viruses: genome-wide screening technology based on the CRISPR system.Frontiers in microbiology · 2024Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The majority of clinically approved drugs target proteins that are secreted or cell surface bound. However, further advances in this area have been hindered by the challenging nature of receptor deorphanization, as there are still many secreted and cell-bound proteins with unknown binding partners. Here, we developed an advanced screening platform that combines CRISPR-CAS9 guide-mediated gene activation (CRISPRa) and high-avidity bead-based selection. The CRISPRa platform incorporates serial enrichment and flow cytometry-based monitoring, resulting in substantially improved screening sensitivity for well-known yet weak interactions of the checkpoint inhibitor family. Our approach has successfully revealed that siglec-4 exerts regulatory control over T cell activation through a low affinity trans-interaction with the costimulatory receptor 4-1BB. Our highly efficient screening platform holds great promise for identifying extracellular interactions of uncharacterized receptor-ligand partners, which is essential to develop next-generation therapeutics, including additional immune checkpoint inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.