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.© The American Society of Gene & Cell Therapy.

Multifunctional aptamer-miRNA conjugates for targeted cancer therapy

Santamaria G.;
2014-01-01

Abstract

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.© The American Society of Gene & Cell Therapy.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/81197
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