Double-stranded genomic DNA (dsDNA)

Double-stranded genomic DNA (dsDNA) is the fundamental repository of genetic information in living organisms, consisting of two complementary strands of nucleotides organized into chromosomes. In the context of modern gene-editing therapeutics, specific sequences within the dsDNA, referred to as guide-defined loci, are targeted to treat or cure genetic diseases. These therapies, such as CRISPR-Cas9, use a guide RNA to direct a nuclease to a precise genomic location where it creates a double-strand break or performs chemical modifications like base editing (Jinek et al., 2012, Science). This interaction triggers cellular repair mechanisms like non-homologous end joining or homology-directed repair, allowing for the permanent alteration of the genetic code to silence or correct pathogenic genes. Targeting dsDNA is a revolutionary strategy for addressing monogenic disorders, including sickle cell disease and hereditary transthyretin amyloidosis, by directly correcting the underlying cause of the disease (Gillmore et al., 2021, NEJM). However, the clinical application of this target involves significant challenges, primarily the risk of off-target editing at non-intended sites and the potential for long-term genomic instability (Fu et al., 2013, Nature Biotechnology).

Other names

Genomic DNATarget DNAChromosomal DNATarget locusProtospacerGuide-defined DNA sequence

Programmable nucleases or base editors utilize guide-directed recognition to induce site-specific double-strand breaks or chemical modifications, enabling gene disruption, correction, or insertion through cellular DNA repair pathways.