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DNA-encoded Libraries of Highly Functionalized Aptamer-like Ligands

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Internal Reference: 2020-033

Market Need聽

While aptamers offer a promising alternative to antibodies due to their stability and ease of synthesis, their broader impact is limited by the narrow chemical diversity of natural nucleotides. This restricted chemical space reduces their ability to engage challenging targets such as protein-protein interactions. Existing strategies to chemically modify aptamers are constrained by enzymatic compatibility, limiting the scope and diversity of non-natural building blocks than can be incorporated.

Technology Overview

We have developed a novel type of DNA-encoded library (DEL) in which the ligands are aptamer-like molecules (鈥渁lenomers鈥�). Unlike conventional DELs, these alenomers can explore targets that are typically inaccessible and are designed with improved features compared to standard aptamers.

visual explanation of the invention topic

Aptamers are very powerful as antibody substitutes, in both therapy and diagnostics. Our technology allows for the augmentation of the 鈥榓lphabet鈥� of aptamers beyond 4 DNA bases, creating DELs of alenomers with full freedom in their chemical modifications, as each modification is encoded by a DNA code. This approach generates molecules diversity-superior to antibodies, while also improving their selectivity, binding strength, and nuclease resistance all without the enzymatic compatibility limitations of traditional aptamer discovery.

Commercial Advantages

  • Libraries of hundreds of thousands of ligands, incorporating diverse monomers rather than the small-molecule ligands typical of DELs
  • Exploration of a novel chemical space (totally non-conventional chemistry for DEL)
  • Structural diversity equivalent or superior to that of antibodies
  • Incorporation of monomers that improve nuclease resistance compared to regular aptamer building blocks
  • DELs of alenomers can be applied broadly to discover new therapeutics for previously inaccessible targets

Additional Information

  • Researcher: Hanadi Sleiman and Maureen McKeague
  • 笔补迟别苍迟蝉:听US 18/001,023 (Filed),聽Canada聽CA 3,186,48w (Filed)聽
  • Publications of work:
    • ChemRxiv. 2022,
  • 碍别测飞辞谤诲蝉:听Platform, Drug Delivery, Synthesis Methods, Therapeutic, Research Tool
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