TY - JOUR
T1 - Design Considerations for RNA Spherical Nucleic Acids (SNAs)
AU - Barnaby, Stacey N.
AU - Perelman, Grant A.
AU - Kohlstedt, Kevin L.
AU - Chinen, Alyssa B.
AU - Schatz, George C.
AU - Mirkin, Chad A.
N1 - Funding Information:
This material is based upon work supported by AFOSR Award FA9550-11-1-0275, Department of Defense National Security Science and Engineering Faculty Fellowship award N00014-15- 1-0043, the Alliance for Cancer Gene Therapy, the NTU-NU Institute for NanoMedicine located at the International Institute for Nanotechnology, Northwestern University, USA and the Nanyang Technological University, Singapore.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/9/21
Y1 - 2016/9/21
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.bioconjchem.6b00350
DO - 10.1021/acs.bioconjchem.6b00350
M3 - Article
C2 - 27523252
AN - SCOPUS:84988504507
VL - 27
SP - 2124
EP - 2131
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 9
ER -