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Highly Parallelized Screening of Functionally Enhanced XNA Aptamers in Uniform Hydrogel Particles
E J Yik1, E Medina1, B M Paegel1,2
1Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California 92697-3958, United States.
ACS Synthetic Biology
|July 6, 2023
Summary
Researchers developed a new method to quickly test Xeno-nucleic acid (XNA) aptamers for biomedical uses. This approach speeds up the discovery of effective XNA aptamer sequences for diagnostics and therapeutics.
Area of Science:
- Biotechnology
- Molecular Biology
- Synthetic Biology
Background:
- Xeno-nucleic acid (XNA) aptamers are non-natural genetic polymers with significant potential for diagnostics and therapeutics.
- Current methods for purifying and testing XNA aptamer sequences are time-consuming and costly, hindering discovery.
Purpose of the Study:
- To develop a rapid and efficient method for surveying the binding properties of XNA aptamers.
- To accelerate the discovery of highly active XNA aptamer motifs for biomedical applications.
Main Methods:
- Preparation of XNA aptamer particles by encapsulating multiple aptamer copies within magnetic particles in a polyacrylamide gel matrix.
- Screening of aptamer particles using flow cytometry to assess target binding affinity.
- Deduction of structure-activity relationships based on binding data.
Main Results:
- The developed assay allows for the rapid surveying of XNA aptamer binding properties.
- The method enables a single researcher to evaluate 48-96 sequences per day, significantly accelerating secondary screening.
- This approach is generalizable and highly parallelizable.
Conclusions:
- The described method provides a straightforward and efficient approach for XNA aptamer discovery.
- This technique dramatically accelerates the pace of identifying potent XNA aptamers for biomedical applications, overcoming current bottlenecks.

