Aptamer-integrated nucleic acid circuits for biosensing: Classification, challenges and perspectives

Owing to their high programmability and modularity, autonomous enzyme-free nucleic acid circuits are attracting ever-growing interest as signal amplifiers with potential applications in developing highly sensitive biosensing techniques. Besides nucleic acid input, the biosensing scope of aptamer-integrated nucleic acids could be further expanded to non-nucleic targets by integrating nucleic acid circuits with aptamers-a class of functional oligonucleotides with binding capabilities toward specific targets. By coupling upstream target recognition with downstream signal amplification, aptamer-integrated nucleic acid circuits enable aptasensors with increased sensitivity and enhanced performances, which may act as powerful tools in various fields including environment monitoring, personal care, clinical diagnosis, etc. In designing aptamer-integrated nucleic acid circuits, smart integration between aptamer and nucleic acid circuits plays a crucial role in developing reliable circuits with good performances. To date, although there are plenty of published researches adopting aptamer-integrated nucleic acid circuits as amplifiers in biosensing systems, deep discussion or systematic review on rational design strategies for aptamer-integrated nucleic acid circuits is still lacking. To fill this gap, rational aptamernucleic acid circuits integration modes were classified and summarized for the first time based on reviewing the state of art of existing aptamer-integrated nucleic acid circuits. Moreover, theoretical updates in nucleic acid circuits designs and major challenges to be overcome in developing highly sensitive aptamer-integrated nucleic acids based biosensing systems are discussed in this review.