Single-stranded DNA and RNA (ssDNA/ssRNA)

Single-stranded DNA (ssDNA) and RNA (ssRNA) are fundamental biological polymers that serve as critical intermediates in genetic expression and as potent signaling molecules for the innate immune system. In a physiological context, ssRNA functions primarily as messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA) to facilitate the translation of genetic code into proteins, while ssDNA typically appears during DNA replication and repair processes (Takeda et al., 2005, PMID: 15621742). These molecules are also recognized as pathogen-associated molecular patterns (PAMPs) by endosomal Toll-like receptors, specifically TLR7 and TLR8 for ssRNA and TLR9 for unmethylated CpG motifs in ssDNA, which triggers the production of type I interferons and pro-inflammatory cytokines (Krieg, 2002, PMID: 11994456). In pharmacology, single-stranded nucleic acids are targeted through two main avenues: the administration of synthetic oligonucleotide agonists to stimulate immune responses against viruses and tumors, and the use of antisense oligonucleotides (ASOs) designed to bind complementary ssRNA sequences to treat genetic disorders by altering protein production (Crooke et al., 2018, PMID: 29559000). Dysregulation of these pathways or the presence of autoantibodies against ssDNA is closely linked to the pathogenesis of autoimmune conditions such as systemic lupus erythematosus.

Other names

Single-stranded nucleic acidsssDNAssRNAPolynucleotidesOligonucleotides

Drugs targeting single-stranded nucleic acids typically act as agonists of pattern recognition receptors (TLR7, TLR8, or TLR9) to induce innate immunity, or utilize antisense technology to hybridize with specific RNA sequences to modulate splicing, induce RNase H-mediated degradation, or block translation.