Journal
MOLECULAR THERAPY
Volume 22, Issue 6, Pages 1151-1163Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2014.5
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Funding
- CNR
- AICR [11-0075]
- MIUR
- MERIT [RBNE08YFN3_001]
- AIRC [11781]
- Italian Ministry of Economy and Finance [14046, 13345]
- Mary Kay Foundation [033-12]
- NIH/NCI [1R01 CA138503]
- Fondazione Berlucchi
- POR Campania FSE
- Elsa U Pardee Foundation
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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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