Ribozyme-Spherical Nucleic Acids

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

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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
Volume137
Issue number33
DOIs
StatePublished - Aug 14 2015

Fingerprint

Catalytic RNA
Nucleic acids
Nucleic Acids
DNA
RNA
Methyltransferases
Glioblastoma
Protein Methyltransferases
Messenger RNA
Cell- and Tissue-Based Therapy
Proteins
MicroRNAs
DNA Repair
Small Interfering RNA
Transfection
Cell death
Apoptosis
Tumors
Repair
Neoplasms

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Rouge, J. L., Sita, T. L., Hao, L., Kouri, F., Briley, W. E., Stegh, A. H., & Mirkin, C. A. (2015). Ribozyme-Spherical Nucleic Acids. Journal of the American Chemical Society, 137(33), 10528-10531. https://doi.org/10.1021/jacs.5b07104
Rouge, Jessica L. ; Sita, Timothy L. ; Hao, Liangliang ; Kouri, Foteini ; Briley, William E. ; Stegh, Alexander H ; Mirkin, Chad A. / Ribozyme-Spherical Nucleic Acids. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 33. pp. 10528-10531.
@article{bd72e2be209c429ca66f021102885eca,
title = "Ribozyme-Spherical Nucleic Acids",
abstract = "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.",
author = "Rouge, {Jessica L.} and Sita, {Timothy L.} and Liangliang Hao and Foteini Kouri and Briley, {William E.} and Stegh, {Alexander H} and Mirkin, {Chad A}",
year = "2015",
month = "8",
day = "14",
doi = "10.1021/jacs.5b07104",
language = "English (US)",
volume = "137",
pages = "10528--10531",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "33",

}

Rouge, JL, Sita, TL, Hao, L, Kouri, F, Briley, WE, Stegh, AH & Mirkin, CA 2015, 'Ribozyme-Spherical Nucleic Acids', Journal of the American Chemical Society, vol. 137, no. 33, pp. 10528-10531. https://doi.org/10.1021/jacs.5b07104

Ribozyme-Spherical Nucleic Acids. / Rouge, Jessica L.; Sita, Timothy L.; Hao, Liangliang; Kouri, Foteini; Briley, William E.; Stegh, Alexander H; Mirkin, Chad A.

In: Journal of the American Chemical Society, Vol. 137, No. 33, 14.08.2015, p. 10528-10531.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ribozyme-Spherical Nucleic Acids

AU - Rouge, Jessica L.

AU - Sita, Timothy L.

AU - Hao, Liangliang

AU - Kouri, Foteini

AU - Briley, William E.

AU - Stegh, Alexander H

AU - Mirkin, Chad A

PY - 2015/8/14

Y1 - 2015/8/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84941649548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941649548&partnerID=8YFLogxK

U2 - 10.1021/jacs.5b07104

DO - 10.1021/jacs.5b07104

M3 - Article

C2 - 26271335

AN - SCOPUS:84941649548

VL - 137

SP - 10528

EP - 10531

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 33

ER -

Rouge JL, Sita TL, Hao L, Kouri F, Briley WE, Stegh AH et al. Ribozyme-Spherical Nucleic Acids. Journal of the American Chemical Society. 2015 Aug 14;137(33):10528-10531. https://doi.org/10.1021/jacs.5b07104