Genomic DNA at the programmed target locus (Target DNA)

Genomic DNA at the programmed target locus refers to the specific chromosomal sequence that is intentionally selected for modification by gene-editing technologies such as CRISPR-Cas9, Zinc Finger Nucleases (ZFNs), or TALENs (Jinek et al., 2012). This target serves as the fundamental repository of genetic information, and its precise sequence dictates the expression of proteins necessary for cellular function (UniProt Consortium, 2023). In many genetic diseases, such as sickle cell disease or transthyretin amyloidosis, mutations at these loci are the underlying cause of pathology (Gillmore et al., 2021). Therapeutic agents are designed to bind to these specific DNA sequences to induce double-strand breaks or chemical modifications, which then trigger cellular repair mechanisms to either knock out a gene or correct a mutation. For instance, exagamglogene autotemcel targets the BCL11A enhancer in genomic DNA to increase fetal hemoglobin production (FDA, 2023). While this approach offers the potential for permanent cures, it also presents significant challenges, including the risk of off-target editing and genomic instability. Consequently, the safety and efficacy of targeting genomic DNA depend heavily on the specificity of the delivery system and the precision of the editing machinery.

Other names

Target DNAProgrammed genomic locusTargeted DNA sequenceGenomic target siteProtospacer sequence

Site-specific DNA modification via programmable nucleases