Activation of Therapeutic Functionalities with Chimeric RNA/DNA Nanoparticles for Treatment of Cancer, Viruses and Other Disease
Posted Nov 05 2012 7:00pm
Description of Invention: A new strategy based on RNA/DNA hybrid nanoparticles, which can be generally used for triggering multiple functionalities inside diseased cells is presented. Individually, each of the hybrids is functionally inactive and functional representation can only be activated by the re-association of at least two cognate hybrids simultaneously present in the same cell. Overall, this novel approach allows (i) the triggered release of therapeutic siRNAs or miRNAs inside the diseased cells, (ii) activation of other split functionalities (e.g. FRET, different aptamers, rybozymes, split proteins) intracellularly, (iii) higher control over targeting specificity (e.g. if two hybrids are decorated with two different tissue specific recognition moieties), (iv) biosensing and tracking of the delivery and re-association of these hybrids in real-time inside cells, (v) increasing the number of functionalities by introducing a branched hybrid structure, (vi) introduction of additional functionalities without direct interference of siRNA processivity, (vii) 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.), (viii) conditional release of all functionalities.
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 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 10nm
Increased specificity for selecting cells of interest using more than one target gene
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Severcan I, et al. "Computational and Experimental RNA Nanoparticle Design," in Automation in Genomics and Proteomics: An Engineering Case-Based Approach, ed. G Alterovitz , et al. (Hoboken: Wiley Publishing, 2009), 193-220. [Book Chapter]
Shapiro B, et al. "Protocols for the In silico Design of RNA Nanostructures," in Nanostructure Design Methods and Protocols, ed. E Gazit, R Nussinov. (Totowa, NJ: Humana Press, 2008), 93-115. [Book Chapter]
Collaborative Research Opportunity: 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. For collaboration opportunities, please contact John Hewes, Ph.D. at email@example.com .
For Licensing Information Please Contact: John Stansberry Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: firstname.lastname@example.org Phone: 301-435-5236 Fax: 301-402-0220