RRM
2008 Rustbelt RNA Meeting
RRM
|
|
|
|
|
Poster abstracts
Abstract:
It has been demonstrated that pRNA, a component of a switchable imitating DNA-packaging motor, can be used as a building block for bottom-up assembly in nanotechnology. The pRNA's structural versatility, coupled with its ability to form dimers, trimers, hexamers, and patterned superstructures via the interaction of two interlocking loops, makes it a promising tool for nanomachine fabrication, pathogen detection, and gene delivery. The presentation will focus on the approaches and methods for construction of multivalent therapeutic pRNA nanoparticles. The construction was based on the bottom-up assembly step by step with controllable structure and stoichiometry. The resulted polyvalent pRNA complex can deliver up to six kinds of therapeutics to specific cancer or viral infected cells as well as ailing cells involved in genetic diseases. Incubation of the RNA nanoparticles containing receptor-binding aptamer or folate resulted in cell binding and the transport of the chimeric pRNA/siRNA, pRNA/ribozyme, or drugs into cells subsequently causing gene silencing, modulating programmed cell death, or inhibiting viral replication. The efficiency was confirmed in animal trials. RNA 3-D design, circular permutation, folding energy alteration, and nucleotide modification were applied to generate stable RNA nanoparticles with low toxicity and to make the chimeric RNA complexes processed into siRNA by Dicer after delivery. Using such protein-free nanoparticles as therapeutic reagents would allow for long-term administration to avoid the induction of antibody due to repeated treatment of chronic diseases.
Keywords: phi29 DNA-packaging motor, therapeutic pRNA nanoparticles, bottom-up assembly
