Ribozyme-Spherical Nucleic Acids

被引：52

作者：

Rouge, Jessica L. ^{[1
,2
]}

Sita, Timothy L. ^{[2
,3
,4
]}

Hao, Liangliang ^{[2
,3
]}

Kouri, Fotini M. ^{[2
,4
]}

Briley, William E. ^{[2
,3
]}

Stegh, Alexander H. ^{[2
,4
,5
]}

Mirkin, Chad A. ^{[1
,2
]}

机构：

[1] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA

[2] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA

[3] Northwestern Univ, Interdisciplinary Biol Sci Grad Program, Evanston, IL 60208 USA

[4] Northwestern Univ, Brain Tumor Inst, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[5] Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2015年 / 137卷 / 33期

基金：

美国国家卫生研究院;

关键词：

HAMMERHEAD RIBOZYMES; SERUM STABILITY; MESSENGER-RNA; MGMT GENE; GLIOBLASTOMA; DELIVERY; CELLS; OLIGONUCLEOTIDES; NANOPARTICLES; TEMOZOLOMIDE;

D O I：

10.1021/jacs.5b07104

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：10528 / 10531

页数：4

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