Development of a Lung Cancer Therapeutic Based on the Tumor Suppressor MicroRNA-34

被引：543

作者：

Wiggins, Jason F. ^{[1
]}

Ruffino, Lynnsie ^{[1
]}

Kelnar, Kevin ^{[1
]}

Omotola, Michael ^{[1
]}

Patrawala, Lubna ^{[1
]}

Brown, David ^{[1
]}

Bader, Andreas G. ^{[1
]}

机构：

[1] Mirna Therapeut Inc, Austin, TX 78744 USA

来源：

CANCER RESEARCH | 2010年 / 70卷 / 14期

关键词：

IN-VITRO; CYTOKINE PRODUCTION; SYNTHETIC SIRNA; CELL-LINES; MIR-34A; P53; APOPTOSIS; EXPRESSION; GROWTH; MICE;

D O I：

10.1158/0008-5472.CAN-10-0655

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor suppressor microRNAs (miRNA) provide a new opportunity to treat cancer. This approach, "miRNA replacement therapy," is based on the concept that the reintroduction of miRNAs depleted in cancer cells reactivates cellular pathways that drive a therapeutic response. Here, we describe the development of a therapeutic formulation using chemically synthesized miR-34a and a lipid-based delivery vehicle that blocks tumor growth in mouse models of non-small-cell lung cancer. This formulation is effective when administered locally or systemically. The antioncogenic effects are accompanied by an accumulation of miR-34a in the tumor tissue and downregulation of direct miR-34a targets. Intravenous delivery of formulated miR-34a does not induce an elevation of cytokines or liver and kidney enzymes in serum, suggesting that the formulation is well tolerated and does not induce an immune response. The data provide proof of concept for the systemic delivery of a synthetic tumor suppressor mimic, obviating obstacles associated with viral-based miRNA delivery and facilitating a rapid route for miRNA replacement therapy into the clinic. Cancer Res; 70(14); 5923-30. (C) 2010 AACR.

引用

页码：5923 / 5930

页数：8

共 44 条

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