Albumin genomic locus (ALB) (ALB)

The Albumin genomic locus (ALB) is a highly transcriptionally active region in hepatocytes responsible for producing serum albumin, the most abundant protein in human plasma. In advanced gene therapy applications, this locus is utilized as a 'safe harbor' or a high-expression site for the site-specific integration of therapeutic genes, such as methylmalonyl-CoA mutase (MMUT). By employing promoterless viral vectors and homologous recombination—a technology known as GeneRide—the therapeutic MMUT gene is inserted directly into the ALB locus. This allows the transgene to be driven by the powerful endogenous albumin promoter, ensuring high-level, liver-specific expression of the missing enzyme. This approach is particularly beneficial for treating methylmalonic acidemia (MMA), a severe metabolic disorder, as it provides a durable therapeutic effect even in the growing livers of pediatric patients. Clinical candidates like LB-001 target this locus to restore metabolic flux and reduce the accumulation of toxic metabolites (LogicBio Therapeutics, 2021; Barzel et al., Nature, 2015). The strategy minimizes the risk of random integration and leverages the liver's natural protein-synthetic machinery to achieve therapeutic protein levels (NCT04581785).

Other names

ALB locusAlbumin geneHuman serum albumin locusHSA locus

Site-specific gene integration via homologous recombination (GeneRide technology) where a promoterless therapeutic transgene is inserted into the endogenous albumin locus to leverage its high transcriptional activity.