Journal article
Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers
Nucleic acids research, Vol.40(13), pp.6319-6337
07/2012
DOI: 10.1093/nar/gks294
PMCID: PMC3401474
PMID: 22467215
Abstract
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.
Details
- Title: Subtitle
- Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers
- Creators
- Kristina W Thiel - Department of Internal MedicineLuiza I Hernandez - Department of Internal MedicineJustin P Dassie - Department of Internal MedicineWilliam H Thiel - Department of Internal MedicineXiuying Liu - Department of Internal MedicineKatie R Stockdale - Department of Internal MedicineAlissa M Rothman - Department of Internal MedicineFrank J Hernandez - Department of Internal MedicineJames O McNamara - Department of Internal MedicinePaloma H Giangrande - Department of Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Nucleic acids research, Vol.40(13), pp.6319-6337
- Publisher
- Oxford University Press
- DOI
- 10.1093/nar/gks294
- PMID
- 22467215
- PMCID
- PMC3401474
- ISSN
- 0305-1048
- eISSN
- 1362-4962
- Language
- English
- Date published
- 07/2012
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Obstetrics and Gynecology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984094559302771
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