Aptamers are short, single-stranded nucleic acids—typically ~20–100 nucleotides—that fold into defined 3D shapes and bind targets (proteins, small molecules, ions, cells) with high affinity and specificity. They are often described as “chemical antibodies,” but they behave differently: their binding comes from nucleic-acid folding + surface complementarity, and their performance is tightly linked to sequence chemistry, structure, and degradation pathways. When your core question is “DNA aptamers or RNA aptamers?”, the best answer is not a slogan. It’s a decision based on (1) structural needs, (2) stability environment, (3) manufacturability, (4) modification strategy, and (5) application constraints. 1) The Fundamental Difference: Structural Vocabulary vs Environmental Toughness RNA aptamers: richer folding vocabulary RNA has a 2′-OH group on the ribose, which expands hydrogen-bonding possibilities and supports a larger “structural vocabulary” (hairpins, internal loops, bulges, pseudoknots, complex tertiary contacts). In practice, this often means more diverse and intricate 3D conformations, which can translate into excellent binding performance for some targets. Takeaway: Choose RNA when the target demands highly nuanced shape recognition (e.g., challenging protein surfaces or structured RNA targets). DNA aptamers: generally more chemically stable and simpler DNA lacks the 2′-OH group and is typically more resistant to base-catalyzed…
