Discovery and translation of functional nucleic acids for clinically diagnosing infectious diseases: Opportunities and challenges

Functional nucleic acids (FNAs) are short, single-stranded nucleic acids that can be derived from synthetic nucleic acid libraries using test-tube selection experiments. Due to their excellent chemical stability, high binding affinities and specificities, compatibility with a variety of signal-transduction mechanisms, and ease of synthesis and modification, FNAs have a great potential to overcome some of the limitations of current pathogen diagnostic methods by acting as molecular recognition elements (MREs) for point-of-care testing. This review summarizes the development of FNA-based biosensors for viral and bacterial detection in clinical samples. We first discuss examples of selecting FNAs for recognizing biomarkers of viral and bacterial pathogens. This is followed by discussion on integrating FNAs into fluorescent, colorimetric, and electrochemical biosensors and applying these sensors towards clinically diagnosing infectious diseases caused by many important bacterial and viral pathogens. Finally, the challenges of making FNA-based biosensors for infectious diseases are provided.