Oligo-Adenine Derived Secondary Nucleic Acid Frameworks: From Structural Characteristics to Applications

Oligo-adenine (polyA) is primarily known for its critical role in mRNA stability, translational status, and gene regulation. Beyond its biological functions, extensive research has unveiled the diverse applications of polyA. In response to environmental stimuli, single polyA strands undergo distinctive structural transitions into diverse secondary configurations, which are reversible upon the introduction of appropriate counter-triggers. In this review, we systematically summarize recent advances of noncanonical structures derived from polyA, including A-motif duplex, A-cyanuric acid triplex, A-coralyne-A duplex, and T ⋅ A-T triplex. The structural characteristics and mechanisms underlying these conformations under specific external stimuli are addressed, followed by examples of their applications in stimuli-responsive DNA hydrogels, supramolecular fibre assembly, molecular electronics and switches, biosensing and bioengineering, payloads encapsulation and release, and others. A detailed comparison of these polyA-derived noncanonical structures is provided, highlighting their distinctive features. Furthermore, by integrating their stimuli-responsiveness and conformational characteristics, advanced material development, such as pH-cascaded DNA hydrogels and supramolecular fibres exhibiting dynamic structural transitions adapting environmental cues, are introduced. An outlook for future developments is also discussed. These polyA derived, stimuli-responsive, noncanonical structures enrich the arsenal of DNA "toolbox", offering dynamic DNA frameworks for diverse future applications.