Aptamers for SARS-CoV-2: Isolation, Characterization, and Diagnostic and Therapeutic Developments

In this review, we are proud to share the incredible work done globally in developing aptamers for the COVID-19 pandemic. Given their desirable characteristics as molecular recognition elements, nucleic acid aptamers were of significant interest to multiple labs worldwide over the past few years. Our review paper features a comprehensive comparison between the most notable SARS-CoV-2 aptamers, taking a detailed look at the SELEX strategies, sequence alignments, secondary structures, and multimeric engineering achievements. We also highlight the application of these aptamers as ligands for therapeutic agents and biosensor development. Overall, aptamers represent a compelling solution to the diagnostic and therapeutic challenges of COVID-19, and we hope this review propels further aptamer research for current and future pandemics.
Read more about the paper here: https://doi.org/10.1002/anse.202200012

-Ryan

Nucleic-Acid-Based Electrochemical Biosensors for Clinical Applications

We are excited to announce our recent review paper on the use of nucleic acids in electrochemical biosensors in collaboration with the Dr. Soleymani lab. Nucleic acids have unique structural motifs that allow them to bind non-nucleic acid targets (aptamers) and catalyze chemical reactions (DNAzymes), making them excellent candidates for use in biosensors. This review paper highlights the historical evolution of nucleic acids as probes in electrochemical biosensors and provides specific examples of their use in clinical settings such as infectious disease, cancer, and cardiovascular health. DNA, in particular, has proven to be an ideal biorecognition element and redox reporter probe due to its ability to be easily modified with various functional groups. We hope that our review will serve as a valuable resource for researchers in the field of biosensors and contribute to the development of new diagnostic tools for a wide range of diseases. Read more about it here: https://doi.org/10.1002/anie.202212496

-Zijie

“Three on Three”

Read our latest work on SARS-CoV-2 detection in saliva, where we developed a trimeric aptamer, named TMSA52, for the recognition of SARS-CoV-2 spike protein. The aptamer not only possesses superb binding affinity but is also capable of binding several SARS-CoV-2 spike protein variants with picomolar affinity, as well as pseudotyped lentiviruses expressing SARS-CoV-2 spike protein variants with femtomolar affinity. Using Pd-Ir nanocubes as nanozymes in an enzyme-linked aptamer binding assay (ELABA), TMSA52 was capable of sensitively detecting diverse pseudotyped lentiviruses in pooled human saliva.  The ELABA was also used to test 50 SARS-CoV-2 positive and 60 negative patient saliva samples, providing sensitivity and specificity values of 84.0% and 98.3%, respectively, thus highlighting the potential of TMSA52 for the development of future rapid tests.

Jiuxing Li, Zijie Zhang, Jimmy Gu, Ryan Amini, Alexandria Mansfield, Jianrun Xia, Dawn White, Hannah D. Stacey, Jann C. Ang, Gurpreet Panesar, Alfredo Capretta, Carlos D. M. Filipe, Karen Mossman, Bruno J. Salena, Jonathan Gubbay, Cynthia Balion, Leyla Soleymani, Matthew S. Miller, Deborah Yamamura, John D. Brennan*, and Yingfu Li*. Three on three: Universal and high-affinity molecular recognition of the symmetric homotrimeric spike protein of SARS-CoV-2 with a symmetric homotrimeric aptamer. J. Am. Chem. Soc. 2022, 144, 23465–23473. (DOI: 10.1021/jacs.2c09870, IF: 16.38)

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

Read our recent review on the discovery and translation of functional nucleic acids developed in our lab.

Jiuxing Li§, Zijie Zhang§, Rudi Liu§, Ryan Amini, Bruno J. Salena, and Yingfu Li*. Discovery and translation of functional nucleic acids for clinically diagnosing infectious diseases: opportunities and challenges. TrAC, Trends Anal. Chem. 2023, 158, 116886 (DOI: 10.1016/j.trac.2022.116886, IF: 12.296)

A Universal Aptamer for SARS-CoV-2 Detection

We’re excited to share our latest work on SARS-CoV-2 where we expand on our previous publications and describe an aptamer class that binds all major variants of concern with high affinity. This is an important tool for the development of aptamer based COVID detection technologies that can be specific, sensitive and robust for the detection of current and possibly future variants. Read more about our work here. -Jim

Zhang Z, Li J, Gu J, Amini R, Stacey HD, Ang JC, White D, Filipe CDM, Mossman K, Miller MS, Salena BJ, Yamamura D, Sen P, Soleymani L, Brennan JD, Li Y. A Universal DNA Aptamer that Recognizes Spike Proteins of Diverse SARS-CoV-2 Variants of Concern. Chemistry. 2022 Feb 26:e202200524. doi: 10.1002/chem.202200524. Epub ahead of print. PMID: 35218097.

Aptamers from random sequence space: Accomplishments, gaps and future considerations

Aptamers are nucleic acids that are capable of recognizing target molecules. Over the past 30 years, thousands of aptamers have been discovered by scientists via in vitro selection technique. This review examined the range of targets as well as the affinity and specificity of ~1000 generated aptamers. By comparing the synthetic aptamers with natural riboswitches, protein-based recognition elements, a gap between synthetic aptamers and natural recognition elements was revealed.  A series of ideas for developing better aptamers were proposed to solve the real world problems. We hope these strategies can help aptamers remain high functionality in application environment. Happy reading 😊 – Shuwen Qian

Qian, S.; Chang, D.; He, S.; Li, Y. Aptamers from Random Sequence Space: Accomplishments, Gaps and Future Considerations. Analytica Chimica Acta 2022, 1196, 339511. https://doi.org/10.1016/j.aca.2022.339511

Applying our SARS-CoV-2 Aptamers for Diagnostics

Following up on our recent report of high-affinity DNA aptamers for SARS-CoV-2, we’ve been busy working with our collaborators in the Soleymani Lab and the Biointerfaces Institute to apply them on electrochemical sensors. Read our latest COVID19 paper at Pubmed to learn more about how we achieve high sensitivity detection of SARS-CoV-2 in unprocessed human saliva to pave the way for a rapid and sample diagnostic test.

Facile Synthesis of Pd-Ir Nanocubes for Biosensing

Take a quick look at our recent publication in Frontiers in Chemistry. In this paper, a simple and surfactant-free approach is presented to synthesize Pd-Ir nanocubes with atomic Ir shell thickness in an aqueous solution at room temperature. Biomolecules such as antibodies and nucleic acids have free access to the surface of Pd-Ir nanocubes. Applications of Pd-Ir nanocubes in immunoassays and aptamer-based biosensors are realized, exploiting the excellent peroxidase activity and fluorescence quenching ability of Pd-Ir nanocubes. Read more about our work at Pubmed. – Jiuxing

Li J, Li Y. Facile Synthesis of Pd-Ir Nanocubes for Biosensing. Front Chem. 2021 Nov 24;9:775220. doi: 10.3389/fchem.2021.775220. PMID: 34900937; PMCID: PMC8651546.