Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells
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 li...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2011
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| Online Access: | http://hdl.handle.net/1721.1/65350 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0002-1293-2097 |
| _version_ | 1826216827875753984 |
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| author | Goldberg, Michael Solomon Xing, Deyin Ren, Yin Orsulic, Sandra Sharp, Phillip A. Bhatia, Sangeeta N |
| author2 | Whitaker College of Health Sciences and Technology |
| author_facet | Whitaker College of Health Sciences and Technology Goldberg, Michael Solomon Xing, Deyin Ren, Yin Orsulic, Sandra Sharp, Phillip A. Bhatia, Sangeeta N |
| author_sort | Goldberg, Michael Solomon |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:53:45Z |
| format | Article |
| id | mit-1721.1/65350 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:53:45Z |
| publishDate | 2011 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/653502022-09-29T22:14:09Z Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells Goldberg, Michael Solomon Xing, Deyin Ren, Yin Orsulic, Sandra Sharp, Phillip A. Bhatia, Sangeeta N 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 Sharp, Phillip A. Sharp, Phillip A. Goldberg, Michael Solomon Xing, Deyin Ren, Yin Bhatia, Sangeeta N. 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-Harvard Center for Cancer Nanotechnology Excellence (Grant U54-CA119349) National Cancer Institute (U.S.) Marie D. and Pierre Casimir-Lambert Fund National Cancer Institute (U.S.) (Cancer Center Support (core) Grant P30-CA14051) 2011-08-23T15:01:51Z 2011-08-23T15:01:51Z 2011-01 2010-10 Article http://purl.org/eprint/type/JournalArticle 1091-6490 http://hdl.handle.net/1721.1/65350 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. https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0002-1293-2097 en_US http://dx.doi.org/10.1073/pnas.1016538108 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Goldberg, Michael Solomon Xing, Deyin Ren, Yin Orsulic, Sandra Sharp, Phillip A. Bhatia, Sangeeta N Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells |
| title | Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells |
| title_full | Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells |
| title_fullStr | Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells |
| title_full_unstemmed | Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells |
| title_short | Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival bearing tumors derived from Brca1-deficient ovarian cancer cells |
| title_sort | nanoparticle mediated delivery of sirna targeting parp1 extends survival bearing tumors derived from brca1 deficient ovarian cancer cells |
| url | http://hdl.handle.net/1721.1/65350 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0002-1293-2097 |
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