期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 137, 期 33, 页码 10528-10531出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.5b07104
关键词
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资金
- Center for Cancer Nanotechnology Excellence (CCNE) initiative of National Institutes of Health (NIH) [U54 CA151880]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR060810]
- Defense Advanced Research Projects Agency [HR0011-13-2-0018]
- John McNicholas Foundation
- Pharmaceutical Research and Manufacturers of America Foundation
- Howard Hughes Medical Institute International Predoctoral Fellowship
- National Cancer Institute/National Institutes of Health NRSA Fellowship [F30CA174058-01]
- Ryan Fellowship
Ribozymes are highly structured RNA sequences that can be tailored to recognize and cleave specific stretches of miRNA. 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 O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein involved in chemotherapeutic resistance of solid tumors, foremost glioblastoma multi-forme (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.
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