Human albumin (ALB) locus genomic DNA (ALB locus)

The genomic DNA at the therapeutic integration locus, specifically the human albumin (ALB) gene, serves as a "safe harbor" for the site-specific insertion of a functional alpha-L-iduronidase (IDUA) transgene. This approach is primarily utilized in genome editing therapies for Mucopolysaccharidosis type I (MPS I), a lysosomal storage disorder caused by IDUA deficiency (Sangamo Therapeutics, 2017). By targeting a highly transcriptionally active site like the albumin locus in the liver, the therapy aims to turn the liver into a "biofactory" that continuously produces and secretes the IDUA enzyme into the bloodstream (Ou et al., 2019). The interaction involves sequence-specific nucleases, such as Zinc Finger Nucleases (ZFNs), which create a double-strand break at the locus to facilitate the integration of the donor DNA template via homology-directed repair or non-homologous end joining. This permanent modification of the host genome is designed to provide a lifelong supply of the missing enzyme, potentially offering a curative alternative to chronic enzyme replacement therapy (ClinicalTrials.gov, NCT02702115). However, the strategy requires precise targeting to avoid off-target effects and ensure the long-term safety of the genetic modification.

Other names

Albumin safe harbor locusALB integration siteIntron 1 of the human albumin geneTherapeutic integration site for IDUA

Targeted genomic integration of a functional IDUA transgene via Zinc Finger Nuclease-mediated double-strand breaks at the albumin locus to drive high-level enzyme production in the liver.