ArticleCell discovery2019
A chemical approach for global protein knockdown from mice to non-human primates.
Article in Cell discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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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
60 citing papers in PubMed.
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Engineered autophagy receptors administered with extracellular vesicles eliminate pathological Tau and TDP-43.Nature biomedical engineering · 2026Article
- Antibody-bottlebrush prodrug conjugates for targeted cancer therapy.Nature biotechnology · 2026Article
- Agonist-specific FPR1 conformational change prevents receptor recycling and promotes targeted protein degradation.Acta pharmaceutica Sinica. B · 2026Article
- Charge-reversal proteolysis polymers enable tissue-specific STING degradation in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RuPHOTACs Provide Photocontrol Over Protein Degradation with Optimized Properties for Biological Applications.Research square · 2026Article
- Destabilized calcium dynamics visualized using the genetically-coded probe GCaMPJ in intact hearts of Calstabin2-null mice.Frontiers in physiology · 2026Article
- Photocontrolled trimethoprim PROTACs targeting the eDHFR protein tag.Nature communications · 2025Article
- Context Matters: E3 Ligase-Ligand Pairing Strategies for Optimized PROTAC Performance.Protein & cell · 2025Article
- Novel PROTAC to target FKBP12: the potential to enhance bone morphogenetic protein activity and apoptosis in multiple myeloma.Haematologica · 2025Article
- Methods to accelerate PROTAC drug discovery.The Biochemical journal · 2025Review
- Rapid and sustained degradation of the essential centrosome protein CEP192 in live mice using the AID2 system.Science advances · 2025Article
- Mechanisms underlying dilated cardiomyopathy associated with FKBP12 deficiency.The Journal of general physiology · 2025Article
- Time-dependent effect of FKBP12 loss in the development of dilated cardiomyopathy.The Journal of general physiology · 2025Article
- PROTAC: a revolutionary technology propelling small molecule drugs into the next golden age.Frontiers in oncology · 2025Review
- The AID2 system offers a potent tool for rapid, reversible, or sustained degradation of essential proteins in live mice.bioRxiv : the preprint server for biology · 2024Article
- Chemotherapy-Enabled Colorectal Cancer Immunotherapy of Self-Delivery Nano-PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras.Current topics in medicinal chemistry · 2024Review
- Recent Advances in Optically Controlled PROTAC.Bioengineering (Basel, Switzerland) · 2023Review
- PROTACs: Emerging Targeted Protein Degradation Approaches for Advanced Druggable Strategies.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although conventional genetic modification approaches for protein knockdown work very successfully due to the increasing use of CRISPR/Cas9, effective techniques for achieving protein depletion in adult animals, especially in large animals such as non-human primates, are lacking. Here, we report a chemical approach based on PROTACs technology that efficiently and quickly knocks down FKBP12 (12-kDa FK506-binding) protein globally in vivo. Both intraperitoneal and oral administration led to rapid, robust, and reversible FKBP12 degradation in mice. The efficiency and practicality of this method were successfully demonstrated in both large and small animals (mice, rats, Bama pigs, and rhesus monkeys). Furthermore, we showed this approach can also be applied to effectively knockdown other target proteins such as Bruton's tyrosine kinase (BTK). This chemical protein knockdown strategy provides a powerful research tool for gene function studies in animals, particularly in large animals, for which gene-targeted knockout strategies may remain unfeasible.
Identifiers
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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.