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Primer-Free Aptamer Selection Using A Random DNA Library
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Automated high-throughput selection of DNA aptamers using a common optical next-generation sequencer.

Alissa Drees1, Christian Ahlers1, Timothy Kehrer1

  • 1Hamburg School of Food Science, Institute of Food Chemistry, University of Hamburg, Grindelallee 117, Hamburg 20146, Germany.

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|February 28, 2026
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Summary

This study introduces an automated platform to improve DNA aptamer selection, making the process faster and more effective. The novel method significantly enhances the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process.

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Genomics

Background:

  • Conventional Systematic Evolution of Ligands by Exponential Enrichment (SELEX) for aptamer selection is inefficient, time-consuming, and labor-intensive.
  • Existing SELEX methods have limitations in efficacy and throughput for identifying high-affinity aptamers.

Purpose of the Study:

  • To develop and validate a novel automated high-throughput screening platform to augment DNA aptamer selection.
  • To enhance the efficiency and speed of aptamer discovery compared to traditional SELEX.

Main Methods:

  • Modification of an optical next-generation sequencer's software to enable automated fluorescence-based binding assays.
  • Integration of sequencing with binding assays for real-time screening of displayed DNA sequences.
  • Application of the platform for aptamer selection against Pseudomonas aeruginosa proteins (LecA, LecB, PEA) and other targets.

Main Results:

  • High-affinity DNA aptamers for LecA, LecB, and PEA were identified in only 3-5 SELEX rounds.
  • The automated method yielded aptamers with higher affinity compared to 12 rounds of conventional SELEX.
  • Demonstrated versatility of the platform for aptamer selection against small molecules and whole cells, including a kanamycin-binding aptamer and Escherichia coli.

Conclusions:

  • The automated high-throughput platform significantly enhances SELEX efficacy and reduces selection time to approximately one week.
  • This novel approach offers deeper insights into the aptamer selection process.
  • The platform is adaptable for selecting aptamers against diverse targets, from small molecules to whole cells.