Non-Erythropoietin receptor genomic DNA off-target sites (Non-EPOR off-targets)

Non-Erythropoietin receptor (EPOR) genomic DNA off-target sites are unintended genomic sequences that are inadvertently modified by gene-editing technologies, such as CRISPR-Cas9, designed to target the EPOR gene (Fu et al., 2013, Nature Biotechnology). These sites typically share high sequence homology with the intended EPOR target, leading to non-specific binding and cleavage by the gene-editing machinery (Tsai et al., 2015, Nature Biotechnology). In therapeutic contexts, such as the development of treatments for hematological disorders, these sites are not therapeutic targets but rather significant safety liabilities. Modification of these off-target loci can result in genotoxic effects, including chromosomal translocations or the disruption of tumor suppressor genes, which may lead to cellular transformation (Zhang et al., 2015, Genome Biology). Consequently, identifying and quantifying activity at these sites using high-throughput sequencing methods is a critical requirement for the safety assessment of genomic medicines (Kandul et al., 2016, Scientific Reports). Minimizing these effects is essential for ensuring the precision and clinical viability of any EPOR-related genetic intervention.

Other names

Off-target genomic lociUnintended DNA cleavage sitesNon-specific genomic binding sites

Unintended sequence-specific DNA binding and cleavage leading to mutations or chromosomal rearrangements.