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    [9.13]NS Forum No.172-Update on RNA Nanotechnology for Applications in Therapeutics and Nanomedicine

    Title: Update on RNA Nanotechnology for Applications in Therapeutics and Nanomedicine
    Speaker: Prof. Peixuan Guo
    Host: Profs. Wang chen,Yanlian Yang,,Baoquan Ding, Xing-jie Liang
    Time: 9:40 AM, September 13, 2011 

    Place: Conference Room of fourth floor in NCNST

    Abstract: 

    Living beings produce an assortment of highly-ordered structures and smart nanomachines that are made up of DNA, RNA or protein to carry out diverse functions. These macromolecules have intrinsically defined features at nanometer scale to serve as building-blocks for bottom-up fabrication in nanotechnology. This notion is exemplified by bacteriophage phi29 DNA packaging motor comprised of DNA, RNA and protein. The motor is geared by a hexameric pRNA ring, and a protein connector channel serving as a path for dsDNA. I will describe the use of both pRNA and channel in nanotechnology.

    The robust motor channel was inserted into a lipid bilayer and generated extremely reliable, precise and sensitive conductance signatures when ions or DNA/RNA pass through the channel. Information about the structure, length and conformational dynamics can then be deduced by their characteristic dwell times, current blockades and signature during translocation. The motor exercises a one-way traffic property for dsDNA. Receptors were introduced within the channel inner wall for detecting the binding of analytes to measured real time current signature to detect biomolecules or chemicals at extremely low concentrations in the presence of many contaminants. This robust channel with one-way traffic has a wide range of applications in biotechnology, disease diagnosis, pathogen detection, homeland security, drug/toxin screening, environmental sensing as well as dsDNA loading and gene delivery in bioreactors, liposomes, or high throughput DNA sequencing apparatus. A lipid monolayer was used to direct the assembly of massive sheets of patterned arrays of reengineered connector channel as making materials in chips for detection and storage. The connector was also assembled into 84 subunit nanoparticles via tags of peptide for 60-subunit and RNA for 60 subunits, a method for incorporating 5-80 assortments of ligands, drugs, markers, or Ab/Ag for multivalent delivery or signal enhancement.

    RNA has emerged as a nanotech platform due to its diversity in structure and functions. RNA is unique in comparison to DNA by virtue of its high thermodynamic stability, formation of noncanonical base pairings and stacking. Loops serve as intra- or inter-molecule mounting dovetail. 2-6 nucleotides are sufficient for annealing. Unique features in transcription termination, self-assembly, post-transcription modification, self-processing by spicing or cleavage by cis-ribozymes, and pH-resistance in endosome enable in vivo production of nanoparticles harboring aptamer, siRNA, ribozyme, riboswitch, miRNA for therapy, detection, and regulation. One example is the phi29 pRNA forming dimer, trimer, tetramer, and hexamer via interlocking loops to deliver therapeutics to specific cancer or viral infected cells in animal trials. Using such stable RNA nanoparticles with the favorable features of no-antibody induction, long circulation time, targeted delivery, non-immune response, multivalent nanoparticles with controllable defined structure and stoichiometry allow effective
    repeated treatment of chronic diseases.

    Introduction:

    Dr. Peixuan Guo is the Dane & Mary Louise Miller Endowed Chair Professor of Biomedical Engineering at University of Cincinnati, Director of one NIH Nanomedicine Development Centers and Director of one National Cancer Institute (NCI) Cancer Nanotech Platform Program

    Dr. Guo received his Ph.D. in Microbiology with training in biophysics from the University of Minnesota in 1987; did his postdoc at NIH before joining Purdue University as an assistant professor in 1990, tenured in 1993, full Professor in 1997, and was honored as a Purdue Faculty Scholar in 1998. He was recruited to University of Cincinnati as endowed chair in 2007. 

    He constructed phi29 DNA packaging motor (PNAS, 1986), discovered phi29 motor pRNA (Science, 1987), assembled infectious dsDNA viruses (J Virology, 1995), discovered pRNA hexamer (Mol Cell, 1998), pioneered RNA nanotechnology (Mol Cell, 1998, JNN, 2003; Nano Lett., 2004, 2005; Nature Nanotechnology, 2010). His lab built a dual imaging system to detect single-fluorophores (EMBO J, 2007; RNA, 2007), incorporated the phi29 motor channel into a lipid membrane (Nature Nanotechnology, 2009) for single molecule sensing with potentials for high throughput dsDNA sequencing.

    He received Pfizer Distinguished Faculty Award in 1995; Purdue Faculty Scholar award in 1998; Purdue Seed Award in 2004, 2005, and 2007; the Lions Club Cancer Research Award in 2006; and COV Distinguished Alumni of the University of Minnesota in 2009, Distinguished Research Award in 2010 and 2011. He is editor or board member of five nanotech journals; reported hundreds of times over the radio or TV such as ABC and NBC, and featured in Newsletters of NIH, NSF, MS-NBC, NCI and ScienceNow etc; was a member of two prominent national nanotech initiatives sponsored by NIST, NIH, NSF and National Council of Nanotechnology; panelist of DOD medical assessment workshop; member of the NIH NDC Steering Committee from 2006-2010, member of the review panel (site-visit) of NCI Intramural Research Program in 2010, and member of NIH-NCI Alliance Coordination and Governance Committee, a $150 Million program of Nanotech in Cancer.
    count:
    Copyright © 2011, Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety,
    Chinese Academy of Sciences
    Email: zhao-office@ihep.ac.cn