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Activation of Therapeutic Functionalities With Chimeric RNA/DNA Nanoparticles for Treatment of Cancer, Viruses and Other Diseases


Laboratory: National Cancer Institute

Invention: A new strategy based on RNA/DNA hybrid nanoparticles, which generally can be used to trigger multiple functionalities inside diseased cells, is presented. Individually, each hybrid is functionally inactive, and functional representation can only be activated by the reassociation of at least two cognate hybrids simultaneously present in the same cell. Overall, this novel approach allows 1) the triggered release of therapeutic siRNAs or miRNAs inside the diseased cells, 2) activation of other split functionalities (e.g. FRET, different aptamers, rybozymes, split proteins) intracellularly, 3) higher control over targeting specificity (e.g., if two hybrids are decorated with two different tissue-specific recognition moieties), 4) biosensing and tracking of the delivery and reassociation of these hybrids in real-time inside cells, 5) increasing the number of functionalities by introducing a branched hybrid structure, 6) introduction of additional functionalities without direct interference of siRNA processivity, 7) increasing the retention time in biological fluids by fine-tuning chemical stability through substituting the DNA strands with chemical analogs (e.g., LNA, PNA, etc.), and 8) conditional release of all functionalities.

Commercial Applications:

  • Therapeutic siRNA for cancer, viruses, and other diseases
  • Therapeutic for delivery of multiple functionalities
  • Diagnostic to visualize cancer cells, virus-infected cells, or diseased cells, or to track the delivery and effectiveness of siRNA treatment or other treatments associated with the particle
  • Research tool to study cancer, viral infections, or other diseases


  • Novel way for multiple functionality delivery and activation
  • Enhanced chemical stability and pharmacokinetics due to the average size of nanoparticles exceeding 10 nm
  • Increased specificity for selecting cells of interest using more than one target gene


Licensing and collaboration opportunities may be available. The NCI Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutic RNA/DNA nanoparticles.


View the full listing here (focused on licensing) or here (focused on collaboration).