| http://purl.uniprot.org/citations/35226042 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35226042 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.org/dc/terms/identifier | "doi:10.1084/jem.20211057"xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Harris J.M."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Fang M."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Kim D.J."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Dennis M.S."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Shan L."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Giese T."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Gunasekaran K."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Chan D."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Calvert M.E.K."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Duque J."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Watts R.J."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Lewcock J.W."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Nguyen H.N."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Liang N."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Scearce-Levie K."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Dugas J.C."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Ullman J.C."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Troyer M.D."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Chau R."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Diaz D."xsd:string |
| http://purl.uniprot.org/citations/35226042 | http://purl.uniprot.org/core/author | "Arguello A."xsd:string |