Off-target genomic DNA sites with partial homology to CXCL10 gRNA (CXCL10-OT)

Off-target genomic DNA sites with partial homology to CXCL10 gRNA are unintended sequences within the genome that share high sequence similarity with the target site of the CXCL10 gene. CXCL10, also known as Interferon gamma-induced protein 10 (IP-10), is a chemokine involved in immune cell trafficking and is a focal point for treating inflammatory diseases (UniProt P02778). In CRISPR-Cas9 based therapies, a guide RNA (gRNA) is designed to direct the Cas9 nuclease to the CXCL10 locus; however, the system may also bind to and cleave these off-target sites if they differ by only a few nucleotides (NIH/NHGRI). This lack of absolute specificity can lead to permanent, unintended genetic modifications, including double-strand breaks at non-target loci. Such events pose significant safety risks, such as the potential for chromosomal translocations or the disruption of essential genes and tumor suppressors (PubMed: 26735122). Consequently, these sites are not therapeutic targets but rather critical safety liabilities that must be rigorously identified and minimized during drug development. Techniques like GUIDE-seq and CIRCLE-seq are standardly used to map these off-target interactions to ensure the precision of the gene-editing tool (Nature Biotechnology, 2015). Understanding these sites is vital for biotech analysts to evaluate the genotoxic risk profile of any CRISPR-based intervention targeting CXCL10.

Other names

CXCL10 CRISPR off-target sitesNon-specific CXCL10 gRNA binding sitesGenomic off-targets

Unintended double-strand DNA cleavage and subsequent non-homologous end joining (NHEJ) or homology-directed repair (HDR) at non-target genomic loci with sequence similarity to the intended CXCL10 target (PubMed: 23360773).