Genomic DNA at the Albumin locus (ALB locus)

The Albumin (ALB) locus is a highly transcriptionally active region of the human genome located on chromosome 4 (4q13.3), responsible for producing albumin, the most abundant protein in human serum. In therapeutic contexts, this locus is utilized as a safe harbor or bio-factory site for the integration of therapeutic transgenes via genome editing tools like Zinc Finger Nucleases (ZFNs) (PMID: 26030171). By inserting a promoterless gene into the first intron of the albumin gene, the therapeutic protein is expressed under the control of the powerful endogenous albumin promoter, which is naturally optimized for high-level expression in hepatocytes (Sangamo Therapeutics, 2018). This strategy is primarily employed to treat monogenic disorders such as Hemophilia B and Lysosomal Storage Disorders, including Hunter and Hurler syndromes, by ensuring a steady supply of the missing protein in the bloodstream (NCT02695160). While promising for providing a permanent genetic fix, the approach requires precise DNA cleavage and carries risks of off-target effects or insertional mutagenesis (PMID: 30742115). Clinical development has focused on using Adeno-Associated Virus (AAV) vectors to deliver the editing machinery to the liver (PMID: 31477910).

Other names

Albumin gene locusALB locusAlbumin safe harborHepatocyte albumin locusAlbumin integration site

Site-specific integration of a therapeutic transgene into the albumin locus using Zinc Finger Nucleases (ZFNs) to leverage the endogenous albumin promoter for high-level protein expression.