Ribozyme-Spherical Nucleic Acids

Jessica L. Rouge, Timothy L. Sita, Liangliang Hao, Fotini M. Kouri, William E. Briley, Alexander H. Stegh, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Ribozymes are highly structured RNA sequences that can be tailored to recognize and cleave specific stretches of mRNA. Their current therapeutic efficacy remains low due to their large size and structural instability compared to shorter therapeutically relevant RNA such as small interfering RNA (siRNA) and microRNA (miRNA). Herein, a synthetic strategy that makes use of the spherical nucleic acid (SNA) architecture to stabilize ribozymes and transfect them into live cells is reported. The properties of this novel ribozyme-SNA are characterized in the context of the targeted knockdown of O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein involved in chemotherapeutic resistance of solid tumors, foremost glioblastoma multiforme (GBM). Data showing the direct cleavage of full-length MGMT mRNA, knockdown of MGMT protein, and increased sensitization of GBM cells to therapy-mediated apoptosis, independent of transfection agents, provide compelling evidence for the promising properties of this new chemical architecture.

Original languageEnglish (US)
Pages (from-to)10528-10531
Number of pages4
JournalJournal of the American Chemical Society
Issue number33
StatePublished - Aug 14 2015

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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