Synthesis, physicochemical, and biological evaluation of spherical nucleic acids for RNAi-based therapy in glioblastoma

Serena Tommasini-Ghelfi, Andrew Lee, Chad A. Mirkin, Alexander H. Stegh*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Spherical nucleic acids (SNAs), an emerging class of gene-regulatory nanotherapeutics, typically consist of a nanoparticle core densely functionalized with a shell of radially oriented small interfering RNA (siRNA) oligonucleotides, microRNA (miRNA) mimics, or antagonists. The unique three-dimensional SNA structure regardless of core type (e.g., gold or lipids) confers heightened resistance to nuclease-mediated degradation and accounts for robust cell entry in the absence of auxiliary transfection vehicles. In murine models of glioblastoma (GBM), the most aggressive and prevalent form of malignant brain cancers, systemically administered siRNA or miRNA-conjugated SNAs penetrated blood-brain and blood-tumor barriers and robustly reduced tumor progression. Here, we describe methods for the synthesis and physicochemical and biological characterization of SNA gene silencing effects in glioma cells in vitro and in patient-derived xenograft models in vivo.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages371-391
Number of pages21
DOIs
StatePublished - Jan 1 2019

Publication series

NameMethods in Molecular Biology
Volume1974
ISSN (Print)1064-3745

Keywords

  • Biotherapeutic gene silencing
  • Nanotherapeutic
  • RNA interference
  • Spherical nucleic acids

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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