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| Content Provider | PubMed Central |
|---|---|
| Author | Judge, Adam D. Robbins, Marjorie Tavakoli, Iran Levi, Jasna Hu, Lina Fronda, Anna Ellen, Ambegia Mcclintock, Kevin Maclachlan, Ian |
| Copyright Year | 2009 |
| Abstract | siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in both hepatic and subcutaneous tumor models. This was correlated with target gene silencing following a single intravenous administration that was sufficient to cause extensive mitotic disruption and tumor cell apoptosis. Our siRNA formulations induced no measurable immune response, minimizing the potential for nonspecific effects. Additionally, RNAi-specific mRNA cleavage products were found in tumor cells, and their presence correlated with the duration of target mRNA silencing. Histological biomarkers confirmed that RNAi-mediated gene silencing effectively inhibited the target’s biological activity. This report supports an RNAi-mediated mechanism of action for siRNA antitumor effects, suggesting a new methodology for targeting other key genes in cancer development with siRNA-based therapeutics. |
| Related Links | http://dx.doi.org/10.1172/jci37515 |
| Ending Page | 673 |
| Page Count | 13 |
| Starting Page | 661 |
| File Format | |
| ISSN | 00219738 |
| e-ISSN | 15588238 |
| Journal | The Journal of Clinical Investigation |
| Issue Number | 3 |
| Volume Number | 119 |
| Language | English |
| Publisher | American Society for Clinical Investigation |
| Publisher Date | 2009-03-02 |
| Access Restriction | Open |
| Rights Holder | American Society for Clinical Investigation |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
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