The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice
Open accessAbstract
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.
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Cites
Detection of circulating tumor necrosis factor after endotoxin administration
Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O'Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., & Wilmore, D. W. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806093182301 · Cited by 1,677
RNAi-mediated gene silencing in non-human primates
Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., et al. (2006) · Nature · doi:10.1038/nature04688 · Cited by 1,357
Progress towards in Vivo Use of siRNAs
Behlke, M. A. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.01.001 · Cited by 677
5′-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma
Poeck, H., Besch, R., Maihoefer, C., Renn, M., Tormo, D., Morskaya, S. S., Kirschnek, S., Gaffal, E., Landsberg, J., Hellmuth, J., et al. (2008) · Nature Medicine · doi:10.1038/nm.1887 · Cited by 387
Cited by
Rational design of cationic lipids for siRNA delivery
Semple, S. C., Akinc, A., Chen, J., Sandhu, A. P., Mui, B. L., Cho, C. K., Sah, D. W. Y., Stebbing, D., Crosley, E. J., Yaworski, E., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1602 · Cited by 1,822
Self-citationTherapeutic siRNA silencing in inflammatory monocytes in mice
Leuschner, F., Dutta, P., Gorbatov, R., Novobrantseva, T. I., Donahoe, J. S., Courties, G., Lee, K. M., Kim, J. I., Markmann, J. F., Marinelli, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1989 · Cited by 839
The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery
Cheng, X., & Lee, R. J. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.01.022 · Cited by 703
Silencing disease genes in the laboratory and the clinic
Watts, J. K., & Corey, D. R. (2012) · The Journal of Pathology · doi:10.1002/path.2993 · Cited by 470
Polymeric nanostructured materials for biomedical applications
Tang, Z., He, C., Tian, H., Ding, J., Hsiao, B. S., Chu, B., & Chen, X. (2016) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2016.05.005 · Cited by 363
Metadata
- Authors
- Judge, A. D., Robbins, M., Tavakoli, I., Levi, J., Hu, L., Fronda, A., Ambegia, E., McClintock, K., & MacLachlan, I.
- Venue
- Journal of Clinical Investigation
- Published
- 2009-03-02
- Volume
- 119
- Issue
- 3
- Pages
- 661-673
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2120421571
- Cited by
- 336
- References
- 4
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Judge, A. D., Robbins, M., Tavakoli, I., Levi, J., Hu, L., Fronda, A., Ambegia, E., McClintock, K., & MacLachlan, I. (2009). Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice. Journal of Clinical Investigation. https://doi.org/10.1172/jci37515
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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