oligodeoxynucleotides

Oligodeoxynucleotides (ODNs) are short, single-stranded DNA molecules, typically 12 to 25 nucleotides in length, produced synthetically from deoxyribonucleotides with a phosphodiester backbone. They bind with sequence-specificity to complementary DNA or RNA targets and are used as research reagents and, in some cases, as therapeutic agents. In diagnostics and molecular biology, ODNs serve as primers for PCR and sequencing, as probes in hybridization assays, and as components of DNA capture sequences in microarrays and various detection systems.

Chemistry and modifications play a central role in ODN function. To enhance stability and affinity, backbones and sugars are modified. Common backbones include phosphorothioate linkages; sugar modifications such as 2'-O-methyl or 2'-O-mly helps resist nucleases and improve binding. More robust approaches use locked nucleic acids (LNA) or other modifications. Some ODNs function as antisense oligonucleotides (ASOs) designed to modulate gene expression, either by recruiting RNase H to degrade the target RNA or by steric blocking of translation or splicing.

Applications encompass diagnostics, therapeutics, and basic research. Therapeutic antisense oligonucleotides are designed to target specific mRNA sequences to downregulate or modify expression; several ASOs have been developed for clinical use. ODNs can also form DNA aptamers—short DNA sequences that bind proteins with high affinity—or act as antisense probes in functional studies.

Delivery and safety considerations affect in vivo use. Challenges include cellular uptake, nuclease stability, potential immunostimulation (for example via unmethylated CpG motifs), and off-target effects, which drive ongoing development of chemical modifications and delivery strategies.