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Delivery of chemo-s...
Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers
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- Thiel, Kristina W. (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- Hernandez, Luiza I. (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- Dassie, Justin P. (författare)
- 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
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- Thiel, William H. (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- Liu, Xiuying (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- Stockdale, Katie R. (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- Rothman, Alissa M. (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- Hernandez, Frank J (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- McNamara, James O. (författare)
- Department of Internal Medicine, University of of Iowa, Iowa City, IA 52242, United States
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- Giangrande, Paloma H. (författare)
- 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
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(creator_code:org_t)
- 2012-03-30
- 2012
- Engelska.
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Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 40:13, s. 6319-6337
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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).
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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Thiel, Kristina ...
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Hernandez, Luiza ...
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Dassie, Justin P ...
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Thiel, William H ...
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Liu, Xiuying
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Stockdale, Katie ...
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visa fler...
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Rothman, Alissa ...
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Hernandez, Frank ...
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McNamara, James ...
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Giangrande, Palo ...
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