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Multifunctional Aptamer-miRNA Conjugates for Targeted Cancer Therapy
Open accessAbstract
While microRNAs (miRNAs) clearly regulate multiple pathways integral to disease development and progression, the lack of safe and reliable means for specific delivery of miRNAs to target tissues represents a major obstacle to their broad therapeutic application. Our objective was to explore the use of nucleic acid aptamers as carriers for cell-targeted delivery of a miRNA with tumor suppressor function, let-7g. Using an aptamer that binds to and antagonizes the oncogenic receptor tyrosine kinase Axl (GL21.T), here we describe the development of aptamer-miRNA conjugates as multifunctional molecules that inhibit the growth of Axl-expressing tumors. We conjugated the let-7g miRNA to GL21.T and demonstrate selective delivery to target cells, processing by the RNA interference machinery, and silencing of let-7g target genes. Importantly, the multifunctional conjugate reduced tumor growth in a xenograft model of lung adenocarcinoma. Therefore, our data establish aptamer-miRNA conjugates as a novel tool for targeted delivery of miRNAs with therapeutic potential.
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Cites
Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth
Mahlknecht, G., Maron, R., Mancini, M., Schechter, B., Sela, M., & Yarden, Y. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1302594110 · Cited by 169
Cited by
The delivery of therapeutic oligonucleotides
Juliano, R. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw236 · Cited by 854
Nimjee, S. M., White, R. R., Becker, R. C., & Sullenger, B. A. (2017) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104558 · Cited by 607
Aptamer Nanomedicine for Cancer Therapeutics: Barriers and Potential for Translation
Lao, Y.-H., Phua, K. K. L., & Leong, K. W. (2015) · ACS Nano · doi:10.1021/nn507494p · Cited by 259
The Roles of MicroRNAs in Breast Cancer
Takahashi, R.-U., Miyazaki, H., & Ochiya, T. (2015) · Cancers · doi:10.3390/cancers7020598 · Cited by 116
Metadata
- Authors
- Esposito, C. L., Cerchia, L., Catuogno, S., De Vita, G., Dassie, J. P., Santamaria, G., Swiderski, P., Condorelli, G., Giangrande, P. H., & de Franciscis, V.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 22
- Issue
- 6
- Pages
- 1151-1163
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2024682947
- Cited by
- 169
- References
- 1
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Esposito, C. L., Cerchia, L., Catuogno, S., De Vita, G., Dassie, J. P., Santamaria, G., Swiderski, P., Condorelli, G., Giangrande, P. H., & de Franciscis, V. (2014). Multifunctional Aptamer-miRNA Conjugates for Targeted Cancer Therapy. Molecular Therapy. https://doi.org/10.1038/mt.2014.5
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