ArticleACS chemical biology2024
Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein-Protein Interaction.
Article in ACS chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Identification of affinity-optimized peptide binders of a viral protease for chemical genetic applications.Bioorganic & medicinal chemistry letters · 2026Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Beyond amyloid: nanobody-mediated neuroinflammatory therapy for Alzheimer's disease.Translational neurodegeneration · 2025Review
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
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Authors and funding
18 authors.
Funding
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Abstract
A versatile, safe, and effective small-molecule control system is highly desirable for clinical cell therapy applications. Therefore, we developed a two-component small-molecule control system based on the disruption of protein-protein interactions using minocycline, an FDA-approved antibiotic with wide availability, excellent biodistribution, and low toxicity. The system comprises an anti-minocycline single-domain antibody (sdAb) and a minocycline-displaceable cyclic peptide. Here, we show how this versatile system can be applied to OFF-switch split CAR systems (MinoCAR) and universal CAR adaptors (MinoUniCAR) with reversible, transient, and dose-dependent suppression; to a tunable T cell activation module based on MyD88/CD40 signaling; to a controllable cellular payload secretion system based on IL12 KDEL retention; and as a cell/cell inducible junction. This work represents an important step forward in the development of a remote-controlled system to precisely control the timing, intensity, and safety of therapeutic interventions.
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