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Activation of different functionalities inside target cells through auto-recognizing therapeutic R/DNA chimeric hybrids: a novel approach in therapeutic RNA nanotechnology

Thursday, October 11, 2012 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center, Building 45



* FARE Award Winner


  • KA Afonin
  • M Viard
  • AN Martins
  • SJ Lockett
  • AE Maciag
  • EO Freed
  • MA Dobrovolskaya
  • E Heldman
  • L Jaeger
  • R Blumenthal
  • BA Shapiro


Using RNA interference (RNAi) as a therapeutic agent it is routinely possible to knock down the expression of target genes in diseased cells. One of the ways to initiate the RNAi machinery is through the direct exogenous introduction to the cells of small interfering RNA (siRNA) duplexes. Herein, we present a new strategy based on therapeutic RNA/DNA hybrids which can be generally used for triggering the RNAi pathway as well as other functionalities inside the diseased cells. Individually, each of the hybrids is functionally inactive and the therapeutic siRNA representation can only be activated by the re-association of at least two cognate hybrids simultaneously present in the same cell. Interestingly, for siRNA release, cognate hybrids can be co-delivered to the cell either on the same or on two different days. This approach opens a new route in development of auto- recognizing “smart” nucleic acids based nanoparticles for a wide range of applications in biomedical RNA nanotechnology.

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