We report on a unique DNA aptamer, denoted MSA52, that displays universally high affinity for the spike proteins of wildtype SARS‐CoV‐2 as well as the Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron variants. Using an aptamer pool produced from round 13 of selection against the S1 domain of the wildtype spike protein, we carried out one‐round SELEX experiments using five different trimeric spike proteins from variants, followed by high‐throughput sequencing and sequence alignment analysis of aptamers that formed complexes with all proteins. A previously unidentified aptamer, MSA52, showed Kd values ranging from 2 to 10 nM for all variant spike proteins, and also bound similarly to variants not present in the reselection experiments. This aptamer also recognized pseudotyped lentiviruses (PL) expressing eight different spike proteins of SARS‐CoV‐2 with Kd values between 20 and 50 pM, and was integrated into a simple colorimetric assay for detection of multiple PL variants. This discovery provides evidence that aptamers can be generated with high affinity to multiple variants of a single protein, including emerging variants, making it well‐suited for molecular recognition of rapidly evolving targets such as those found in SARS‐CoV‐2.
A unique DNA aptamer, denoted MSA52, displays universally high affinity for the spike proteins of the wild‐type SARS‐CoV‐2 as well as its Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron variants. This aptamer also recognizes pseudotyped lentiviruses expressing eight different spike proteins of SARS‐CoV‐2 with very high affinity, exhibiting dissociation constants (Kd) of 20–50 pM for these viruses. More information can be found in the Research Article by J. D. Brennan, Y. Li et al. (DOI: 10.1002/chem.202200078).
Nucleic acids are remarkable molecules. In addition to Watson-Crick base pairing, the different structural motifs of these molecules can bind non-nucleic acid targets or catalyze chemical reactions. Additionally, nucleic acids are easily modified with different molecules or functional groups. These properties make nucleic acids, particularly DNA, ideally suited for use in electrochemical biosensors, both as biorecognition elements and redox reporter probes. In this Minireview, we will review the historical evolution of nucleic acids as probes in electrochemical biosensors. We will then review the specific examples of nucleic-acid-based biosensors that have been evaluated for clinical use in the areas of infectious disease, cancer, or cardiovascular health.
What is the most significant result of this study?This study reports on au nique DNA aptamer,d enoted MSA52, that displays auniversally high affinityfor the spike proteins of wildtype SARS-CoV-2 as well as the Alpha, Beta, Gamma, Epsilon, Kappa, Delta, and Omicron variants. This aptamer also recognizes pseudotyped lentiviruses (PL) expressing eight different spike proteins of SARS-CoV-2 with K d values between 20-50 pM. It was integrated into as imple colorimetric assay for the detection of multiple PL variants. This discovery provides evidence that aptamers can be generated with high affinity to multiple variants of asingle protein, including emerging variants, making them well-suited for molecular recognition of rapidly evolving targets such as those found in SARS-CoV-2.
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