ArticleNature communications2023
DNA framework-engineered chimeras platform enables selectively targeted protein degradation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Unraveling the secrets of novel PROTACs to improve degradation efficacy.Molecular diversity · 2026Review
- Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Proteolysis-targeting chimera (PROTAC) nanomedicines toward cancer treatment: From synthesis to therapeutic delivery.Biomaterials · 2026Review
- Extracellular vesicle-based targeted protein degradation platform for multiple extracellular proteins.EMBO molecular medicine · 2026Article
- In vivo self-assembled nano-PROTAC for the dual degradation of AR and HSP90 to overcome castration-resistant prostate cancer resistance.Signal transduction and targeted therapy · 2025Article
- Article
- DNA-Templated Spatially Controlled Proteolysis Targeting Chimera for Cyclin D1-CDK4/6 Complex Protein Degradation.Journal of the American Chemical Society · 2025Article
- Nanoparticle-Mediated Targeted Protein Degradation: An Emerging Therapeutics Technology.Angewandte Chemie (International ed. in English) · 2025Review
- YY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer in mice.Nature communications · 2025Article
- Review
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Bifunctional Peptide Nanofibrils for Targeted Protein Degradation.Angewandte Chemie (International ed. in English) · 2024Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A challenge in developing proteolysis targeting chimeras (PROTACs) is the establishment of a universal platform applicable in multiple scenarios for precise degradation of proteins of interest (POIs). Inspired by the addressability, programmability, and rigidity of DNA frameworks, we develop covalent DNA framework-based PROTACs (DbTACs), which can be synthesized in high-throughput via facile bioorthogonal chemistry and self-assembly. DNA tetrahedra are employed as templates and the spatial position of each atom is defined. Thus, by precisely locating ligands of POI and E3 ligase on the templates, ligand spacings can be controllably manipulated from 8 Å to 57 Å. We show that DbTACs with the optimal linker length between ligands achieve higher degradation rates and enhanced binding affinity. Bispecific DbTACs (bis-DbTACs) with trivalent ligand assembly enable multi-target depletion while maintaining highly selective degradation of protein subtypes. When employing various types of warheads (small molecules, antibodies, and DNA motifs), DbTACs exhibit robust efficacy in degrading diverse targets, including protein kinases and transcription factors located in different cellular compartments. Overall, utilizing modular DNA frameworks to conjugate substrates offers a universal platform that not only provides insight into general degrader design principles but also presents a promising strategy for guiding drug discovery.
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Registered trials
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