Adeno-associated virus integration site 1 (AAVS1)

Adeno-associated virus integration site 1 (AAVS1) is a specific genomic locus located on human chromosome 19 (19q13.42) that serves as a preferred site for the integration of the adeno-associated virus (AAV) genome [1, 2]. It is widely recognized as a "safe harbor" for gene therapy and genome editing because it resides in a transcriptionally active region with an open chromatin structure, allowing for stable and robust expression of integrated transgenes [6, 13]. The locus is situated within the first intron of the PPP1R12C gene, which encodes the protein phosphatase 1 regulatory subunit 12C, also known as myosin binding subunit 85 (MBS85) [3, 14]. While integration at this site is generally considered to have minimal impact on cellular phenotype, some studies suggest that disruption of the PPP1R12C gene may influence cellular processes such as contractile force [14]. AAVS1 is frequently targeted using site-specific nucleases like CRISPR-Cas9, Zinc Finger Nucleases (ZFNs), and TALENs to treat various monogenic disorders, such as Chronic Granulomatous Disease, by ensuring predictable transgene behavior and reducing the risk of insertional mutagenesis [11, 15].

Other names

AAVS1PPP1R12CProtein phosphatase 1 regulatory subunit 12CMBS85Myosin binding subunit 85

Site-specific genomic integration of therapeutic transgenes into a transcriptionally active locus to ensure stable expression and minimize insertional mutagenesis.