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Delivery of chemo-s...
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Thiel, Kristina W.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
(författare)
Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
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2012-03-30
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Oxford University Press,2012
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LIBRIS-ID:oai:DiVA.org:liu-143338
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-143338URI
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https://doi.org/10.1093/nar/gks294DOI
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Språk:engelska
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Sammanfattning på:engelska
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Human epidermal growth factor receptor 2 (HER2) expression in breast cancer is associated with an aggressive phenotype and poor prognosis, making it an appealing therapeutic target. Trastuzumab, an HER2 antibody-based inhibitor, is currently the leading targeted treatment for HER2+-breast cancers. Unfortunately, many patients inevitably develop resistance to the therapy, highlighting the need for alternative targeted therapeutic options. In this study, we used a novel, cell-based selection approach for isolating cell-type specific, cell-internalizing RNA ligands (aptamers) capable of delivering therapeutic small interfering RNAs (siRNAs) to HER2-expressing breast cancer cells. RNA aptamers with the greatest specificity and internalization potential were covalently linked to siRNAs targeting the anti-apoptotic gene, Bcl-2. We demonstrate that, when applied to cells, the HER2 aptamer-Bcl-2 siRNA conjugates selectively internalize into HER2+-cells and silence Bcl-2 gene expression. Importantly, Bcl-2 silencing sensitizes these cells to chemotherapy (cisplatin) suggesting a potential new therapeutic approach for treating breast cancers with HER2+-status. In summary, we describe a novel cell-based selection methodology that enables the identification of cell-internalizing RNA aptamers for targeting therapeutic siRNAs to HER2-expressing breast cancer cells. The future refinement of this technology may promote the widespread use of RNA-based reagents for targeted therapeutic applications. © 2012 The Author(s).
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Hernandez, Luiza I.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States(Swepub:liu)luihe46
(författare)
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Dassie, Justin P.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States; Department of Molecular and Cellular Biology Program, University of of Iowa, Iowa City, IA 52242, United States
(författare)
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Thiel, William H.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
(författare)
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Liu, XiuyingDepartment of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
(författare)
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Stockdale, Katie R.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
(författare)
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Rothman, Alissa M.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
(författare)
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Hernandez, Frank JDepartment of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States(Swepub:liu)frahe49
(författare)
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McNamara, James O.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
(författare)
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Giangrande, Paloma H.Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States; Department of Radiation Oncology, University of of Iowa, Iowa City, IA 52242, United States
(författare)
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Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United StatesDepartment of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States; Department of Molecular and Cellular Biology Program, University of of Iowa, Iowa City, IA 52242, United States
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Nucleic Acids Research: Oxford University Press40:13, s. 6319-63370305-10481362-4962
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