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Design and self-assembly of siRNA-functionalized RNA nanoparticles for use in automated nanomedicine

  1. Author:
    Afonin, K. A.
    Grabow, W. W.
    Walker, F. M.
    Bindewald, E.
    Dobrovolskaia, M. A.
    Shapiro, B. A.
    Jaeger, L.

  2. Author Address

    [Afonin, Kirill A.; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Afonin, Kirill A.; Grabow, Wade W.; Walker, Faye M.; Jaeger, Luc] Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA. [Bindewald, Eckart] NCI, Basic Sci Program, SAIC, Frederick Inc, Frederick, MD 21701 USA. [Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.;Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA;shapirbr@mail.nih.gov jaeger@chem.ucsb.edu
    1. Year: 2011
    2. Date: Dec
  2. Journal: Nature Protocols
    1. 6
    2. 12
    3. Pages: 2022-2034
  4. Type of Article: Article
  5. ISSN: 1754-2189
  1. Abstract:

    Individual genes can be targeted with siRNAs. The use of nucleic acid nanoparticles (NPs) is a convenient method for delivering combinations of specific siRNAs in an organized and programmable manner. We present three assembly protocols to produce two different types of RNA self-assembling functional NPs using processes that are fully automatable. These NPs are engineered based on two complementary nanoscaffold designs (nanoring and nanocube), which serve as carriers of multiple siRNAs. The NPs are functionalized by the extension of up to six scaffold strands with siRNA duplexes. The assembly protocols yield functionalized RNA NPs, and we show that they interact in vitro with human recombinant Dicer to produce siRNAs. Our design strategies allow for fast, economical and easily controlled production of endotoxin-free therapeutic RNA NPs that are suitable for preclinical development.

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External Sources

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  2. DOI: 10.1038/nprot.2011.418
  3. View record in Web of Science®
  4. WOS: 000298157100016

Library Notes

  1. Fiscal Year: FY2011-2012
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