Journal
BIOCONJUGATE CHEMISTRY
Volume 27, Issue 9, Pages 2124-2131Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.6b00350
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Funding
- AFOSR [FA9550-11-1-0275]
- Department of Defense National Security Science and Engineering Faculty Fellowship award [N00014-15-1-0043]
- Alliance for Cancer Gene Therapy
- NTU-NU Institute for NanoMedicine located at the International Institute for Nanotechnology, Northwestern University, USA
- Nanyang Technological University, Singapore
- National Cancer Institute of the National Institute of Health [U54 CA151880, U54CA199091]
- National Science Foundation Graduate Research Fellowship
- P.E.O. scholar award
- National Defense and Science Engineering Graduate fellowship
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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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