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Nuclease-Resistant Small-Molecule/DNA Hydrogel

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Internal Reference: 2023-052

Market NeedÌý

One of the greatest barriers to mass production and distribution of therapeutic nucleic acids, particularly RNA-based therapeutics, is the rapid degradation that the materials experience when exposed to biological conditions. Despite the variety of attempted stabilization techniques, the degradation process remains hourly, therefore, improved techniques are needed to stabilize nucleic acids for drug delivery.

Technology Overview

ºÚÁÏÍø±¬³Ô¹Ï has invented a novel noncanonical nucleic acid structure resulting from the interaction of poly(deoxyadenine) (dA) with the small nontoxic molecule cyanuric acid (CA). With three faces mimicking thymine, cyanuric acid acts as a bridge between adenines of three poly-dA strands, coaxing them into a supramolecular polymer triple DNA helix. This structure limits the access of exo- and endonucleases to the DNA and RNA strands, thereby stabilising it from standard degradation processes.

visual explanation of topic related to the invention

The hydrogel’s properties are highly tunable via polyA length and CA modifications enabling rapid self-healing and thixotropy, and it has a high mechanical strength (a record strength for any nucleic acid-based gel). It is responsive to pH, DNA strand displacement, and small molecules, allowing controlled disassembly and cargo release, demonstrating enhanced gene silencing efficiency for encapsulated nucleic acid therapeutics.

Commercial Advantages

  • Protects nucleic acid cargo from nuclease degradation
  • Helps with the delivery and endosomal escape of nucleic acid cargo
  • Simpler synthesis compared to other hydrogels and easy structure assembly
  • Versatile and reversible; allows more possibility in structure and functionality
  • Methods of delivery: injectable hydrogel depot technology, intracellular depot, lipid nanoparticle

Additional Information

  • Researcher: Hanadi Sleiman
  • Patents:ÌýUS 19/152,257 (Filed), Canada CA 3,280,900 (Filed)
  • Publications of work:
    • Lachance-Brais, C. Advanced Science, 2023, 10 (12) 2205713Ìý
    • Lachance-Brais, C. J. Am. Chem. Soc. 2024, 146 (9), 5811
  • Keywords: Composition of Matter, Drug Delivery, Platform
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