Iduronate 2-sulfatase gene (IDS) (IDS)

The genomic DNA locus within the IDS gene encodes the enzyme iduronate 2-sulfatase, which is essential for the lysosomal degradation of glycosaminoglycans (GAGs) such as dermatan sulfate and heparan sulfate (MedlinePlus Genetics, 2020). Mutations in this X-linked gene lead to Hunter syndrome (Mucopolysaccharidosis type II), a progressive multisystem disorder characterized by the accumulation of GAGs in various tissues (NORD, 2023). Targeting the IDS genomic locus is a primary strategy for curative therapies, including gene addition via adeno-associated virus (AAV) vectors and site-specific genome editing using zinc finger nucleases (ZFNs) (Sangamo Therapeutics, 2021). These approaches aim to restore permanent endogenous production of the functional enzyme, potentially overcoming the limitations of lifelong enzyme replacement therapy (PubMed, PMID: 30739031). Clinical candidates like SB-913 have explored in vivo genome editing to insert a functional IDS transgene into the albumin locus, while others like RGX-121 utilize AAV-mediated gene delivery directly to the central nervous system (REGENXBIO, 2024). Monitoring efficacy typically involves measuring GAG levels in urine and cerebrospinal fluid, alongside assessing IDS enzyme activity in the blood (NIH, 2022). Safety concerns for these genomic interventions include potential off-target editing effects, immune reactions to the viral delivery vectors, and the risk of insertional mutagenesis (Nature Communications, 2020).

Other names

IDS geneIduronate-2-sulfatase locusMPS2SIDSMucopolysaccharidosis type II gene

Gene addition or genome editing to restore functional iduronate 2-sulfatase enzyme production.