AAVS1

AAVS1, short for Adeno-Associated Virus Integration Site 1, denotes a locus in the human genome that serves as a commonly used site for targeted DNA integration. The site is located on chromosome 19 at 19q13.42, within intron 1 of the PPP1R12C gene, and is characterized by genomic features that support efficient incorporation of exogenous DNA with relatively predictable expression.

Discovery and use of AAVS1 as a safe harbor have driven the development of genome editing strategies that target this locus. Researchers have engineered various nucleases to cut DNA at AAVS1, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR-Cas systems. After the cut, donor DNA with homology to AAVS1 can be integrated into the genome through cellular repair pathways, enabling stable transgene insertion.

Applications and properties of AAVS1 as a safe harbor are widespread in research. It is used to generate engineered human pluripotent stem cells and other cell lines for studies requiring stable, long-term transgene expression with limited positional effects. While AAVS1 serves as a convenient integration site, it is not without caveats: integration can affect nearby gene regulation, expression may vary by cellular context, and off-target editing depends on the chosen nuclease system.

Limitations and considerations emphasize that AAVS1 is a useful but not universally perfect solution for gene insertion. Ongoing research examines long-term outcomes, potential impacts on PPP1R12C function, and any unintended genomic interactions to better define its safety profile in different cell types and applications.