Genomic DNA at intended editing locus (gDNA) (gDNA)

Genomic DNA at the intended editing locus refers to the specific sequence of nucleotides within a cell's genome that is targeted for modification by gene-editing technologies such as CRISPR-Cas9, Zinc Finger Nucleases (ZFNs), or Transcription Activator-Like Effector Nucleases (TALENs). This target serves as the blueprint for cellular function, and its precise alteration allows for the correction of pathogenic mutations, the silencing of deleterious genes, or the insertion of therapeutic sequences (NIH, 2017). In therapeutic applications, the gene-editing machinery recognizes this locus through Watson-Crick base pairing or protein-DNA interactions to induce a double-strand break or chemical modification (Nature, 2019). The biological outcome depends on the cell's endogenous repair mechanisms, such as non-homologous end joining (NHEJ) or homology-directed repair (HDR), which resolve the break to achieve the desired genetic change. Targeting genomic DNA is central to treating various genetic disorders, including sickle cell disease and transthyretin amyloidosis, by addressing the root cause of the disease at the molecular level (FDA, 2023). However, the therapeutic use of this target requires careful monitoring for off-target effects and unintended chromosomal rearrangements to ensure long-term safety (Science, 2018).

Other names

Target DNA sequenceGenomic locusTarget siteProtospacerTargeted genomic region

Site-specific genomic modification via double-strand break induction, base editing, or prime editing followed by cellular DNA repair mechanisms such as non-homologous end joining (NHEJ) or homology-directed repair (HDR).