ArticleThe Journal of experimental medicine2022
Molecular architecture determines brain delivery of a transferrin receptor-targeted lysosomal enzyme.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 82 citations in OpenAlex.
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- CD98hc-targeted antibody shuttles for central nervous system delivery with broad cross-species reactivity.Nature biomedical engineering · 2026Article
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- Transferrin-modified multicomponent liposomes encapsulating paclitaxel-loadedInternational journal of pharmaceutics: X · 2026Article
- Extracellular vesicles released from blood-brain barrier endothelial cells mediate brain iron accumulation during LPS-induced brain inflammation.The Journal of biological chemistry · 2026Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Intranasal delivery route for neurodegenerative diseases: recent insights and future directions.Drug delivery and translational research · 2026Review
- Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood-brain barrier transport.Signal transduction and targeted therapy · 2025Article
- Novel transferrin receptor-mediated enzyme replacement therapy efficiently treats myogenic and neurogenic aspects of Pompe disease in mice.Molecular therapy. Methods & clinical development · 2025Article
- Cracking the Blood-Brain Barrier Code: Rational Nanomaterial Design for Next-Generation Neurological Therapies.Pharmaceutics · 2025Review
- Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- The effects of dose, valency, and affinity on TfR-mediated brain delivery in vivo.Fluids and barriers of the CNS · 2025Article
- Utilization of nanotechnology to surmount the blood-brain barrier in disorders of the central nervous system.Materials today. Bio · 2025Review
- Using Immunoliposomes as Carriers to Enhance the Therapeutic Effectiveness of Macamide N-3-Methoxybenzyl-Linoleamide.Neurology international · 2025Article
- Article
- CYpHER: catalytic extracellular targeted protein degradation with high potency and durable effect.Nature communications · 2024Article
- Insulin-inspired hippocampal neuron-targeting technology for protein drug delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Neurological glycogen storage diseases and emerging therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
Corrections and comments
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Authors and funding
33 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delivery of biotherapeutics across the blood-brain barrier (BBB) is a challenge. Many approaches fuse biotherapeutics to platforms that bind the transferrin receptor (TfR), a brain endothelial cell target, to facilitate receptor-mediated transcytosis across the BBB. Here, we characterized the pharmacological behavior of two distinct TfR-targeted platforms fused to iduronate 2-sulfatase (IDS), a lysosomal enzyme deficient in mucopolysaccharidosis type II (MPS II), and compared the relative brain exposures and functional activities of both approaches in mouse models. IDS fused to a moderate-affinity, monovalent TfR-binding enzyme transport vehicle (ETV:IDS) resulted in widespread brain exposure, internalization by parenchymal cells, and significant substrate reduction in the CNS of an MPS II mouse model. In contrast, IDS fused to a standard high-affinity bivalent antibody (IgG:IDS) resulted in lower brain uptake, limited biodistribution beyond brain endothelial cells, and reduced brain substrate reduction. These results highlight important features likely to impact the clinical development of TfR-targeting platforms in MPS II and potentially other CNS diseases.
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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.