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Literature summary for 3.1.6.13 extracted from

  • Lu, J.Z.; Boado, R.J.; Hui, E.K.; Zhou, Q.H.; Pardridge, W.M.
    Expression in CHO cells and pharmacokinetics and brain uptake in the Rhesus monkey of an IgG-iduronate-2-sulfatase fusion protein (2011), Biotechnol. Bioeng., 108, 1954-1964.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
diagnostics sulfatases are potential therapeutic biopharmaceuticals Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
the recombinant fusion enzyme protein is triaged to the lysosomal compartment of MPS-II fibroblasts, expression in CHO cells as IgG-sulfatase fusion protein with the enzyme fused to a genetically engineered monoclonal antibody against the human insulin receptor, i.e. HIRMAb. The cDNA encoding the human IDS cDNA, minus the sequence encoding the signal peptide, is fused to the carboxyl terminus of the CH3 region of the heavy chain of the chimeric HIRMAb Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information to deliver the enzyme across the human blood-brain barrier, the sulfatase is re-engineered as an IgG-sulfatase fusion protein with a genetically engineered monoclonal antibody against the human insulin receptor. The human insulin receptor monoclonal antibody HIRMAb part of the HIRMAb-IDS fusion protein acts as a molecular Trojan horse to ferry the fused IDS across the blood-brain barrier, overview. The HIRMAb-IDS fusion protein is tritiated and injected intravenously into the adult Rhesus monkey at a low dose of 0.1 mg/kg. The IDS enzyme activity in plasma is elevated 10fold above the endogenous level, and therapeutic plasma concentrations are generated in vivo. The uptake of the HIRMAb-IDS fusion protein in the brain is sufficiently high to produce therapeutic concentrations of IDS in the brain following IV administration of the fusion protein Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Synonyms

Synonyms Comment Organism
IDS
-
Homo sapiens

General Information

General Information Comment Organism
malfunction mucopolysaccharidosis, MPS, type II is caused by mutations in the lysosomal enzyme, iduronate-2-sulfatase. MPS-II affects the brain and enzyme replacement therapy is ineffective for the brain, because the enzyme does not cross the blood-brain barrier Homo sapiens