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

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.

SUBMITTER: Afonin KA

PROVIDER: S-EPMC3498981 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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

Afonin Kirill A KA Grabow Wade W WW Walker Faye M FM Bindewald Eckart E Dobrovolskaia Marina A MA Shapiro Bruce A BA Jaeger Luc L

Nature protocols 20111201 12

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 ...[more]

PMID: 22134126

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