期刊
BIOCONJUGATE CHEMISTRY
卷 27, 期 9, 页码 2124-2131出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.6b00350
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资金
- 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
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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