Albumin (ALB) locus (ALB)

The Albumin (ALB) locus in hepatocytes is the molecular target for the LNP1265 delivery system, which is a component of the REGV131-LNP1265 gene therapy (NCT06379789). This system utilizes CRISPR-Cas9 to create a site-specific double-strand break within the first intron of the ALB gene, allowing for the targeted insertion of a promoter-less Coagulation Factor IX (F9) transgene. By placing the F9 gene under the control of the powerful endogenous albumin promoter, the liver can produce high levels of functional Factor IX protein to treat Hemophilia B. This gene insertion approach aims to provide a permanent cure, especially in pediatric populations where liver growth would otherwise dilute non-integrating viral vectors. LNP1265 specifically delivers the gene-editing components (Cas9 mRNA and sgRNA) to hepatocytes, while the DNA template is typically delivered via an AAV vector. Potential challenges include ensuring genomic precision to avoid off-target effects and managing the immune response to the delivery vehicles and the Cas9 protein.

Other names

Serum albumin geneALB geneAlbumin promoterAlbumin first intron

CRISPR-Cas9-mediated site-specific gene insertion into the Albumin locus to drive transgene expression via the endogenous albumin promoter.