Open AccessThe effector mechanism of siRNA spherical nucleic acids
Author(s) -
Gokay Yamankurt,
Robert J. Stawicki,
Diana M. Posadas,
Joseph Q. Nguyen,
Richard W. Carthew,
Chad A. Mirkin
Publication year - 2020
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1915907117
Subject(s) - gene knockdown , small interfering rna , rna interference , effector , nucleic acid , microbiology and biotechnology , mechanism (biology) , rna , gene silencing , microrna , biology , gene expression , chemistry , gene , biochemistry , epistemology , philosophy
Significance Although small interfering RNAs (siRNAs) are promising agents for treating many diseases, cellular delivery difficulties have prevented their widespread application. The use of spherical nucleic acids (SNAs) as single-entity gene regulation agents could overcome this limitation, since SNAs naturally and rapidly enter over 50 cell types. Consequently, siRNA-SNAs have been extensively used for effecting knockdown in both research and clinical settings. However, the mechanism of gene regulation by siRNA-SNAs is not well understood. Herein, we study cytosolic processing of siRNA-SNAs and how it leads to gene knockdown. Informed by this mechanism, we designed an SNA architecture with an order-of-magnitude-higher siRNA density. Importantly, this higher density reduces the cellular toxicity of SNAs without loss in RNA interference performance.
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