Ribozyme鈥揝pherical Nucleic Acids

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• 作者：Jessica L. Rouge ; Timothy L. Sita ; Liangliang Hao ; Fotini M. Kouri ; William E. Briley ; Alexander H. Stegh ; Chad A. Mirkin
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：August 26, 2015
• 年：2015
• 卷：137
• 期：33
• 页码：10528-10531
• 全文大小：293K
• ISSN：1520-5126

文摘

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鈭扴NA are characterized in the context of the targeted knockdown of Op>6p>-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.