Albumin gene first intron (ALB Intron 1)

The Albumin gene first intron is a specific non-coding DNA sequence within the human ALB gene, which encodes the most abundant protein in human plasma. In the context of modern biotherapeutics, this site is utilized as a genomic safe harbor for the targeted insertion of therapeutic genes, particularly in the liver (Sangamo Therapeutics). By using genome editing tools such as Zinc Finger Nucleases (ZFNs), a promoterless transgene can be integrated into this intron, allowing it to be expressed under the control of the highly active endogenous albumin promoter (Sharma et al., 2015). This strategy is designed to provide a permanent, high-output source of therapeutic proteins, such as clotting factors or lysosomal enzymes, to treat systemic genetic diseases (ClinicalTrials.gov, NCT02695160). Clinical applications have focused on conditions like Hemophilia B and Mucopolysaccharidosis, where the goal is to achieve stable, long-term protein production from a small fraction of hepatocytes without compromising overall liver function. While the intron itself does not code for a protein, its strategic location allows for stable expression without significantly disrupting the production of native albumin (PubMed: 26437753).

Other names

ALB locusAlbumin safe harborAlbumin intron 1Human serum albumin gene first intron

Zinc Finger Nuclease (ZFN)-mediated site-specific integration of a therapeutic transgene into the endogenous albumin locus to leverage the high-strength albumin promoter for systemic protein expression (Sharma et al., 2015; Sangamo Therapeutics).