Deoxyribonucleic acid and Ribonucleic acid (DNA and RNA) (DNA/RNA)

Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA) are the fundamental biopolymers that store and execute the genetic program of all living organisms (Lodish et al., Molecular Cell Biology, 2016). DNA serves as the primary repository of genetic information, while various RNA species mediate the translation of this information into proteins and regulate gene expression. In pharmacology, DNA is a classic target for cytotoxic chemotherapy, where agents induce structural damage to trigger apoptosis in malignant cells (Pommier et al., Chem. Rev. 2009). RNA has emerged as a versatile therapeutic target through the development of antisense oligonucleotides and RNA interference (RNAi) drugs, which allow for the sequence-specific knockdown or modification of disease-associated proteins (Crooke et al., Nat. Rev. Drug Discov. 2018). Because these molecules are essential for all cellular life, drugs targeting them must often balance potent efficacy with significant risks of genotoxicity and systemic toxicity.

Other names

Nucleic acidsGenetic materialGenomic DNACellular RNADeoxyribonucleic acidRibonucleic acid

Drugs targeting nucleic acids operate through diverse mechanisms: DNA-damaging agents like alkylators (e.g., cisplatin) and intercalators (e.g., doxorubicin) create physical lesions or disrupt helical structure to inhibit replication and transcription (Pommier et al., 2016). Antimetabolites (e.g., 5-fluorouracil) mimic natural nucleotides to cause chain termination upon incorporation. RNA-targeted therapies, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), utilize sequence-specific hybridization to trigger mRNA degradation via RNase H or the RISC complex, or to modulate pre-mRNA splicing (Crooke et al., 2018). Additionally, certain antivirals act as nucleoside analogs to inhibit viral RNA-dependent RNA polymerases (Beigel et al., 2020).