Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells
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Goldberg-2011-Jan-Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells.pdf
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Author(s)
Goldberg, Michael Solomon
Xing, Deyin
Ren, Yin
Orsulic, Sandra
Sharp, Phillip A.
Bhatia, Sangeeta N
Date Issued
January 2011
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Goldberg, M. S. et al. “Nanoparticle-mediated Delivery of siRNA Targeting Parp1 Extends Survival of Mice Bearing Tumors Derived from Brca1-deficient Ovarian Cancer Cells.” Proceedings of the National Academy of Sciences 108.2 (2010) : 745-750. ©2011 by the National Academy of Sciences.
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Final published version
Abstract
Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) with small molecules has been shown to be an effective treatment for ovarian cancer with BRCA mutations. Here, we report the in vivo administration of siRNA to Parp1 in mouse models of ovarian cancer. A unique member of the lipid-like materials known as lipidoids is shown to deliver siRNA to disseminated murine ovarian carcinoma allograft tumors following intraperitoneal (i.p.) injection. siParp1 inhibits cell growth, primarily by induction of apoptosis, in Brca1-deficient cells both in vitro and in vivo. Additionally, the treatment extends the survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells but not from Brca1 wild-type cells, confirming the proposed mechanism of synthetic lethality. Because there are 17 members of the Parp family, the inherent complementarity of RNA affords a high level of specificity for therapeutically addressing Parp1 in the context of impaired homologous recombination.
MIT Department
Whitaker College of Health Sciences and Technology
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1073/pnas.1016538108
