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<p>Effective subset selection from complex oligonucleotide libraries is crucial for genomics, synthetic biology, and DNA data storage. The polymerase chain reaction, foundational for amplifying target subsets is limited by primer design and length for specificity, which constrains the scalability of oligo libraries and increases the synthesis burden for primers. We introduce an oligo subset selection methodology that utilizes sequence-specific cyclic nucleotide synthesis and blocking of the template oligos. This approach eliminates the need for primers for selective hybridization and enables the encoding and selection of hundreds of subsets with barcode lengths of fewer than five nucleotides. Moreover, cyclic selection enables a hierarchical data structure in the oligo library, enhancing the programmability. This advancement offers a scalable and cost-effective solution for handling complex oligo libraries.</p>

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Oligonucleotide subsets selection by single nucleotide resolution barcode identification

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月12日

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  • Woojin Kim,
  • Mingweon Chon,
  • Yoonhae Koh,
  • Hansol Choi,
  • Eunjin Choi,
  • Hyewon Park,
  • Yushin Jung,
  • Taehoon Ryu,
  • Sunghoon Kwon,
  • Yeongjae Choi

摘要

Effective subset selection from complex oligonucleotide libraries is crucial for genomics, synthetic biology, and DNA data storage. The polymerase chain reaction, foundational for amplifying target subsets is limited by primer design and length for specificity, which constrains the scalability of oligo libraries and increases the synthesis burden for primers. We introduce an oligo subset selection methodology that utilizes sequence-specific cyclic nucleotide synthesis and blocking of the template oligos. This approach eliminates the need for primers for selective hybridization and enables the encoding and selection of hundreds of subsets with barcode lengths of fewer than five nucleotides. Moreover, cyclic selection enables a hierarchical data structure in the oligo library, enhancing the programmability. This advancement offers a scalable and cost-effective solution for handling complex oligo libraries.