ABSTRACT

Aldurazyme (laronidase) is a form of recombinant human α-L-iduronidase (rhIDU) developed as an enzyme replacement therapy for the rare recessive genetic disorder, mucopolysaccharidosis I. The rhIDU enzyme is normally located and active in the lysosome, where it participates in the sequential enzymatic degradation process of certain glycosaminoglycans. The specific development of Aldurazyme began with the cloning of the human rhIDU complementary DNA (cDNA) in 1991 that allowed the development of recombinant Chinese hamster ovary (CHO) cells that overexpress and secrete the human rhIDU enzyme. rhIDU is produced using a cDNA copy of the human rhIDU mRNA message that is overexpressed in recombinant CHO cells. The complete tertiary structure for rhIDU has not been determined by X-ray crystallography, although there are structure models proposed using predictive rules based on primary enzyme sequence. The rhIDU coding sequence has many polymorphisms that have a modest effect on the normal enzyme in general.