Design Considerations for RNA Spherical Nucleic Acids (SNAs)

Autor: Kevin L. Kohlstedt, Alyssa B. Chinen, Stacey N. Barnaby, Chad A. Mirkin, George C. Schatz, Grant A. Perelman
Rok vydání: 2016
Předmět:
Zdroj: Bioconjugate Chemistry
ISSN: 1520-4812
1043-1802
DOI: 10.1021/acs.bioconjchem.6b00350
Popis: 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.
Databáze: OpenAIRE