Aptamers for protection against viral infections

The Li Lab, in collaboration with the Miller Lab, has made progress with using aptamers as therapeutics to prevent infections like COVID-19.

A high binding affinity COVID-19 (C19HBA) aptamer was compared to commercial monoclonal antibodies in a pre-clinical study. Results show that testing has been successful in protected the mouse model used in the pre-clinical study from infection as effectively as commercial monoclonal antibodies.

For the story published by McMaster University, click HERE.

The aptamer research described above is partially funded by Zentek Ltd., a technology development and commercialization company. We’re thankful for the collaboration with both the Miller Lab and Zentek Ltd.

For a news release by Zentek Ltd. on initial testing, click HERE.

For a news release by Zentek Ltd. on the aptamer technology platform, click HERE.

For a news release by Zentek Ltd. on the results of the pre-clinical study, click HERE.

New DNAzyme that requires an organic solvent!

Read about our latest RNA-cleaving DNAzyme, one that requires an organic solvent to function!  

Given that many organic molecules are widely used as solvents in synthetic and analytical chemistry, we were motivated to derive a functional DNAzyme in these conditions. While several DNAzymes in literature have been reported to work under organic conditions, no prior study has ever selected for DNAzymes that strictly require an organic solvent to function.  

In this study, using a positive selection in dimethyl sulfoxide (DMSO) and a negative selection in an aqueous solution, we isolated an RNA-cleaving DNAzyme that strictly requires DMSO for its catalytic activity. A minimized, more efficient version of the DNAzyme was then generated, and applied in a proof-of-concept aptazyme system for sensing applications.  

Overall, we continue to be fascinated by the amazing capabilities of in vitro selection and catalytic DNA! Check out the full paper HERE.

Fluorogenic DNAzyme for F. nucleatum detection

Check out our latest DNAzyme, DT4, a trans-acting DNAzyme that can be activated by a thermally stable protein target which is unique to Fusobacterium nucleatum subspecies.

Our interest in detecting this human pathogenic bacterium resides with the fact that F. nucleatum is associated with many poor health conditions, such as gum disease, adverse pregnancy outcomes, and colorectal cancer.

Our efforts in demonstrating that DT4 can function as a fluorescent sensor in both human saliva and stool samples provides the opportunity to develop diagnostic platforms for F. nucleatum since thermally stable targets overcome the nuclease activity in biological samples.

Click HERE for the full paper.

On the Cover

A research article first published in February 2023 on the characterization of diverse DNA aptamers for recognition of COVID-19 has been featured on the cover of the most recent issue (issue #5) of the journal Analysis & Sensing.

We’re all very excited and overjoyed with the recognition of all the hard work that’s being done here in the lab.

For the full article, check out the following link:

Comparative Characterization of Diverse DNA Aptamers for Recognition of Spike Proteins of Multiple SARS-CoV-2 Variants

For more papers, see the Publications page of the website.

Salmonella Detection

Learn about the lab’s recent work on the detection of Salmonella for food safety here https://brighterworld.mcmaster.ca/articles/salmonella-solution-researchers-develop-rapid-test-for-food-contamination/

Angewandte Chemie International Edition has a Press Release for this work:

https://onlinelibrary.wiley.com/page/journal/15213773/homepage/press/202315press.html.

CTV news report our story, “McMaster researchers develop salmonella solution”

https://www.ctvnews.ca/video?clipId=2669669.

Jiuxing Li, Shadman Khan, Jimmy Gu, Carlos D. M. Filipe*, Tohid F. Didar*, Yingfu Li*. A simple Au-on-Au colorimetric sensor for food-borne pathogen Salmonella typhimurium. Angew. Chem. Int. Ed. 2023, e202300828. (DOI: 10.1002/anie.202300828, IF: 16.8)

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)