Engineered genomic DNA sequence recognized by ARCUS nuclease (ARCUS target site)

The engineered genomic DNA sequence recognized by ARCUS nuclease is the specific nucleotide sequence within a host or viral genome targeted for modification by the ARCUS genome editing platform (Precision BioSciences, 2024). ARCUS is a proprietary technology derived from the naturally occurring I-CreI homing endonuclease, which is re-engineered to recognize a unique 22-base pair DNA sequence (Smith et al., 2006; Grizot et al., 2009). Upon binding, the ARCUS nuclease creates a double-strand break, which the cell repairs via non-homologous end joining (NHEJ) or homology-directed repair (HDR). This process allows for the permanent knockout of deleterious genes, the insertion of therapeutic genes, or the elimination of viral DNA, such as the covalently closed circular DNA (cccDNA) of the Hepatitis B virus (Precision BioSciences, 2023). This target is utilized in various therapeutic pipelines to treat chronic infections, rare genetic diseases, and to engineer allogeneic CAR-T cells for oncology. The high specificity of the nuclease for its target sequence is a key design feature intended to reduce the risk of off-target mutations and associated safety concerns (Jantz et al., 2021).

Other names

ARCUS recognition sequenceMeganuclease target siteI-CreI-derived recognition siteARCUS binding site

Site-specific DNA double-strand break induction followed by cellular DNA repair (NHEJ or HDR) to achieve gene disruption, insertion, or repair.