Genomic off-target loci with partial complementarity to the GJD2 sgRNA

Genomic off-target loci with partial complementarity to the GJD2 sgRNA refer to unintended DNA sequences within the genome that are recognized and potentially modified by a CRISPR-Cas9 system designed to target the GJD2 gene. GJD2, which encodes the gap junction protein Connexin 36, is a target for research in neurological and retinal disorders due to its role in electrical synapses (UniProt P60570). Off-target effects occur when the single guide RNA (sgRNA) binds to sequences that are similar but not identical to the intended target, leading to double-strand breaks at these locations (Fu et al., 2013, Nature Biotechnology). These unintended modifications pose significant safety risks in gene therapy, including the potential for gene silencing, activation of oncogenes, or large-scale chromosomal rearrangements (Kosicki et al., 2018, Nature Biotechnology). Monitoring these loci is a critical component of preclinical safety assessments for any GJD2-directed genetic intervention to ensure therapeutic specificity. Techniques such as GUIDE-seq or in silico prediction are commonly used to identify and quantify the risks associated with these sites (Tsai et al., 2015, Nature Biotechnology).

Other names

GJD2 off-target sitesCRISPR off-targetsUnintended genomic modificationsNon-specific Cas9 binding sites

Unintended DNA cleavage and repair at non-target genomic sites due to sequence similarity with the GJD2-specific sgRNA.