DNL310, or ETV:IDS, is a recombinant form of the iduronate
2-sulfatase enzyme engineered to cross the blood-brain barrier using Denali's proprietary ETV technology.
At various positions, the molecule is modified by a series of interdependent enzymatic reactions that include N-deacetylation of N-acetylated-D-glucosamine, usually followed by N-sulfation, epimerization of D-glucuronic acid into iduronate
, and the addition of sulfate groups at C2 of uronic acid, and at C6 and C3 of glucosamine residues .
Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare lysosomal storage disorder caused by a deficiency of the lysosomal enzyme iduronate
Echeverri-Pena et al., "Laboratory scale production of the human recombinant iduronate
2-sulfate sulfatase-Like from Pichia pastoris" African Journal of Biotechnology, vol.
Children with the disease, also known as MPS Type II, are missing an enzyme called iduronate
Colin lacks an enzyme known as iduronate
sulphatas, which means his body cannot break sugar down properly.
MPS I and MPS II are caused by mutations in the genes encoding alpha-L-iduronidase (IDUA) and iduronate
2-sulfatase (IDS) enzymes, respectively.
In family M, the mother was heterozygous for an iduronate
2-sulfatase (IDS/IDS2) gene rearrangement.
In the study, in a mouse model of MPS II, zinc finger nuclease-mediated genome editing of cells in the liver resulted in expression of therapeutic levels of iduronate
2-sulfatase, an enzyme MPS II patients lack, and in the prevention of metabolic and neurological disease symptoms.
MPS I and MPS II are caused by mutations in the genes encoding alpha-L-iduronidase and iduronate
2-sulfatase enzymes, respectively.