DNAzyme Targeting c-jun Suppresses Skin Cancer Growth
Details
Publication Year 2012-06-20, Volume 4, Issue #139, Page 139ra82
Journal Title
SCIENCE TRANSLATIONAL MEDICINE
Publication Type
Journal Article
Abstract
Worldwide, one in three cancers is skin-related, with increasing incidence in many populations. Here, we demonstrate the capacity of a DNAzyme-targeting c-jun mRNA, Dz13, to inhibit growth of two common skin cancer types-basal cell and squamous cell carcinomas-in a therapeutic setting with established tumors. Dz13 inhibited tumor growth in both immunodeficient and immunocompetent syngeneic mice and reduced lung nodule formation in a model of metastasis. In addition, Dz13 suppressed neovascularization in tumor-bearing mice and zebrafish and increased apoptosis of tumor cells. Dz13 inhibition of tumor growth, which required an intact catalytic domain, was due in part to the induction of tumor immunity. In a series of good laboratory practice-compliant toxicology studies in cynomolgus monkeys, minipigs, and rodents, the DNAzyme was found to be safe and well tolerated. It also did not interfere in more than 70 physiologically relevant in vitro bioassays, suggesting a reduced propensity for off-target effects. If these findings hold true in clinical trials, Dz13 may provide a safe, effective therapy for human skin cancer.
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Keywords
BASAL-CELL CARCINOMA; CD4(+) T-CELLS; DNA ENZYME; IMMUNE-SYSTEM; EXPRESSION; CPG; RNA; ANGIOGENESIS; INHIBITION; MELANOMA
WEHI Research Division(s)
Cancer And Haematology
Rights Notice
© 2013 American Association for the Advancement of Science. All Rights Reserved.


Creation Date: 2012-06-20 12:00:00
Last Modified: 0001-01-01 12:00:00
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