ArticleACS synthetic biology2024
Degron-Based bioPROTACs for Controlling Signaling in CAR T Cells.
Article in ACS synthetic biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed.
- Degrading GPX4 via Biomimetic Nanoparticle-Mediated In Situ Synthesis of Deep-Learning-Designed Binder-Degron Chimeras for Prostate Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- BioPROTACs: a promising approach for targeted protein degradation.Acta pharmacologica Sinica · 2026Review
- Intracellular protein binders for imaging, control and future therapeutics.Nature biomedical engineering · 2026Review
- Emerging biologic modalities for targeted protein degradation.The Journal of biological chemistry · 2026Review
- Identification of affinity-optimized peptide binders of a viral protease for chemical genetic applications.Bioorganic & medicinal chemistry letters · 2026Article
- AI-guided CAR designs and targeted pathway modulation to enhance multi-antigen CAR T cell durability and overcome antigen escape.Nature communications · 2026Article
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- RNA-stabilized coat proteins for sensitive and simultaneous imaging of distinct single mRNAs in live cells.Nature methods · 2026Article
- Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Small molecule- and cell contact-inducible systems for controlling expression and differentiation in mouse embryonic stem cells.Development (Cambridge, England) · 2025Article
- Mitochondrial priming in therapy-induced senescence: implications for CAR-T/NK immunosenolytic therapy.Frontiers in immunology · 2025Review
- Article
- Degron-Based bioPROTACs for Controlling Signaling in CAR T Cells.ACS synthetic biology · 2024Article
- Review
- Proteolysis targeting chimeras (PROTACs) in oncology: a review of patents and regulatory considerations.Pharmaceutical patent analyst · 2024Review
- Transcriptional rewiring in CD8Frontiers in immunology · 2024Review
Corrections and comments
- Update of
Authors and funding
6 authors.
Funding
Abstract
Chimeric antigen receptor (CAR) T cells have made a tremendous impact in the clinic, but potent signaling through the CAR can be detrimental to treatment safety and efficacy. The use of protein degradation to control CAR signaling can address these issues in preclinical models. Existing strategies for regulating CAR stability rely on small molecules to induce systemic degradation. In contrast to small molecule regulation, genetic circuits offer a more precise method to control CAR signaling in an autonomous cell-by-cell fashion. Here, we describe a programmable protein degradation tool that adopts the framework of bioPROTACs, heterobifunctional proteins that are composed of a target recognition domain fused to a domain that recruits the endogenous ubiquitin proteasome system. We develop novel bioPROTACs that utilize a compact four-residue degron and demonstrate degradation of cytosolic and membrane protein targets using either a nanobody or synthetic leucine zipper as a protein binder. Our bioPROTACs exhibit potent degradation of CARs and can inhibit CAR signaling in primary human T cells. We demonstrate the utility of our bioPROTACs by constructing a genetic circuit to degrade the tyrosine kinase ZAP70 in response to recognition of a specific membrane-bound antigen. This circuit can disrupt CAR T cell signaling only in the presence of a specific cell population. These results suggest that bioPROTACs are powerful tools for expanding the CAR T cell engineering toolbox.
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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.