Human albumin locus (ALB) (ALB locus)

The human albumin (ALB) locus, located on chromosome 4q13.3, is a primary hepatic safe-harbor site utilized for site-specific gene integration in liver-directed therapies (Sharma et al., 2015, Blood). It is characterized by its high transcriptional activity, as the liver produces massive quantities of albumin, making it an ideal site to drive the expression of therapeutic proteins like clotting factors or lysosomal enzymes (Manno et al., 2006, Nature Medicine). Therapeutic interventions, such as Zinc Finger Nucleases (ZFNs) developed by Sangamo Therapeutics, are designed to create a double-strand break in the first intron of the ALB gene, allowing for the permanent insertion of a transgene via the cell's natural DNA repair machinery (Ou et al., 2019, Molecular Therapy). This safe harbor approach is intended to provide stable, lifelong protein production while minimizing the risk of insertional mutagenesis associated with random viral integration (Sadelain et al., 2011, Nature Reviews Cancer). Clinical applications have targeted diseases such as Hemophilia B and Mucopolysaccharidosis (MPS) I and II, where the goal is to turn the liver into a bio-factory for the missing protein (ClinicalTrials.gov, NCT02702115). Despite its potential, challenges include ensuring high editing efficiency in vivo and monitoring for off-target effects that could disrupt other critical genomic regions (Ginn et al., 2018, Gene Therapy). The use of the ALB locus as a safe harbor represents a significant shift from traditional gene addition to precise genome editing in the liver (Porteus, 2016, Nature Biotechnology).

Other names

Albumin safe harborHepatic safe-harbor locusALB gene locusHuman ALB locusAlbumin intron 1 safe harbor

Site-specific genomic integration via nuclease-mediated double-strand breaks followed by homology-directed repair (HDR) or non-homologous end joining (NHEJ) to insert a therapeutic transgene under the control of the endogenous albumin promoter (Sharma et al., 2015).