title: Design Considerations for RNA Spherical Nucleic Acids (SNAs).
abstract: Ribonucleic acids (RNAs) are key components in many cellular processes such as cell division, differentiation, growth, aging, and death. RNA spherical nucleic acids (RNA-SNAs), which consist of dense shells of double-stranded RNA on nanoparticle surfaces, are powerful and promising therapeutic modalities because they confer advantages over linear RNA such as high cellular uptake and enhanced stability. Due to their three-dimensional shell of oligonucleotides, SNAs, in comparison to linear nucleic acids, interact with the biological environment in unique ways. Herein, the modularity of the RNA-SNA is used to systematically study structure-function relationships in order to understand how the oligonucleotide shell affects interactions with a specific type of biological environment, namely, one that contains serum nucleases. We use a combination of experiment and theory to determine the key architectural properties (i.e., sequence, density, spacer moiety, and backfill molecule) that affect how RNA-SNAs interact with serum nucleases. These data establish a set of design parameters for SNA architectures that are optimized in terms of stability.
authors: Department of Chemistry and ‡International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors: Stacey N
authors: SN
authors: Barnaby
authors: Department of Chemistry and ‡International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors: Grant A
authors: GA
authors: Perelman
authors: Department of Chemistry and ‡International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors: Kevin L
authors: KL
authors: Kohlstedt
authors: Department of Chemistry and ‡International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors: Alyssa B
authors: AB
authors: Chinen
authors: Department of Chemistry and ‡International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors: George C
authors: GC
authors: Schatz
authors: Department of Chemistry and ‡International Institute for Nanotechnology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors: Chad A
authors: CA
authors: Mirkin
mesh_terms: D001483:Base Sequence; D015195:Drug Design; D006046:Gold / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D020871:RNA Stability; D013499:Surface Properties
chemical_list: D012313:RNA; D006046:Gold