Albumin safe-harbor locus (ALB locus)

The Albumin (ALB) safe-harbor locus is a specific genomic region within the human albumin gene, located on chromosome 4, that serves as a target for site-specific gene integration (Source: NCBI Gene ID 213). It is considered a safe harbor because the albumin gene is extremely active in the liver, allowing for high-level expression of therapeutic proteins without disrupting essential cellular functions (Source: Ou et al., 2019, Molecular Therapy). Therapeutic strategies involve using genome-editing tools, such as Zinc Finger Nucleases (ZFNs), to insert a functional copy of a deficient gene into the albumin locus (Source: Sangamo Therapeutics). This approach leverages the liver's natural capacity to synthesize and secrete large quantities of albumin into the bloodstream, effectively turning the liver into a bio-factory for the missing protein (Source: ClinicalTrials.gov NCT02702115). Clinical applications primarily target monogenic disorders, including Hemophilia B and various Mucopolysaccharidoses (Source: PubMed PMID 26157075). While promising for providing a permanent cure, the use of this locus requires precise targeting to avoid off-target mutations or the disruption of the endogenous albumin production (Source: NIH/GARD). Monitoring of these therapies involves measuring the levels of the newly synthesized protein in the plasma and assessing liver health.

Other names

Albumin gene locusALB locusHuman albumin locusAlbumin safe harbor

Targeted integration of a therapeutic transgene into the endogenous albumin locus via genome editing (e.g., ZFNs, CRISPR/Cas9) to utilize the high transcriptional activity of the albumin promoter for systemic protein production (Source: Sharma et al., 2015, Blood).