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Selective Treatment of Cancer, HIV, Other RNA Viruses and Genetically Related Diseases Using Therapeutic RNA Switches

Posted Nov 05 2012 7:00pm

Description of Invention:

Targeted therapy in cancer or viral infections is a challenge because the disease state manifests itself mainly through differences in the cell interior, for example in the form of the presence of a certain RNAs or proteins in the cytoplasm.

The technology consists of designed RNA switches that activate the RNA interference pathway only in the presence of a trigger RNA or DNA to which they bind, in order to knock down a chosen gene that is not necessarily related to the initial trigger.

This new approach can lead to a new type of drug that has the unique feature of selectively causing a biochemical effect (such as apoptosis) in cells that are infected by RNA viruses (such as HIV), as well as cancer cells. The RNA switch concept can be expanded to selectively treat other genetically related diseases.



Applications:
  • Targeted therapeutic for viral infections, cancer stem cells, and genetically related diseases
  • Research tool to study cancer or viral infection


  • Advantages:
    • Fewer side effects because the therapeutic RNA-interference pathway is only activated by the RNA switch when it is intact and in its active conformation
    • Selectively kills cells infected by RNA viruses
    • Contains a minimal number of single stranded nucleotides, thus minimizing the effects of nucleases


    Development Status:
    In vitro data available

    Inventors:
    Bruce A Shapiro (NCI)
    Eckart HU Bindewald (NCI)
    Kirill A Afonin (NCI)


    Patent Status:
    HHS, Reference No. E-038-2012/0
    US, Application No. 61/561,247 filed 17 Nov 2011
    US, Application No. 61/678,434 filed 01 Aug 2012


    Related Technologies:
    US, Application No. 61/561,257 filed 17 Nov 2011, Reference No. E-039-2012/0


    Relevant Publication:
    1. Afonin KA, et al. [ PMID 23016824 ]
    2. Grabow WW, et al. "RNA Nanotechnology in Nanomedicine," in Nanomedicine and Drug Delivery (Recent Advances in Nanoscience and Nanotechnology), ed. M Sebastian, et al. (New Jersey: Apple Academic Press, 2012), 208-220. [Book Chapter]
    3. Shukla GC, et al. [ PMID 21604810 ]
    4. Afonin KA, et al. [ PMID 22134126 ]
    5. Bindewald E, et al. [ PMID 22067111 ]
    6. Grabow WW, et al. [ PMID 21229999 ]
    7. Kasprzak W, et al. [ PMID 21163354 ]
    8. Afonin KA, et al. [ PMID 20802494 ]
    9. 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]
    10. 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]
    11. Bindewald E, et al. [ PMID 18838281 ]
    12. Yingling YG, Shapiro BA. [ PMID 17616164 ]


    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 switches. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov .


    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: js852e@nih.gov
    Phone: 301-435-5236
    Fax: 301-402-0220


    Ref No: 2495

    Updated: 11/2012

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