TY - JOUR
T1 - Ribozyme-Spherical Nucleic Acids
AU - Rouge, Jessica L.
AU - Sita, Timothy L.
AU - Hao, Liangliang
AU - Kouri, Fotini M.
AU - Briley, William E.
AU - Stegh, Alexander H.
AU - Mirkin, Chad A.
N1 - Publisher Copyright:
© 2015 American Chemical Society.
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
U2 - 10.1021/jacs.5b07104
DO - 10.1021/jacs.5b07104
M3 - Article
C2 - 26271335
AN - SCOPUS:84941649548
SN - 0002-7863
VL - 137
SP - 10528
EP - 10531
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 33
ER -