Bivalent aptamer-dual siRNA chimera is emerging as a new combination therapy

Hongyan Liu

doi:10.14800/rd.1534

Abstract

The selective delivery of siRNAs in a cell type-specific manner represents the major challenge for the application of RNA interference for disease treatment. Aptamers have great potentials as carriers for tumor specific siRNA delivery. With the nature of nucleic acid, aptamers can be ease of modification and editing. Novel bivalent aptamer-dual siRNA chimera (PSMA aptamer- survivin siRNA -EGFR siRNA -PSMA aptamer, PSEP) was developed by fusing two siRNAs (specific to EGFR and survivin) between two PSMA aptamers. Bivalent aptamer offers increased siRNA internalization compared with monovalent counterpart. PSEP chimera is able to inhibit EGFR and survivin simultaneously in a cell type-specific manner. In PSMA expressing tumor xenografts, PSEP significantly inhibits tumor growth and angiogenesis. Our results highlight that co-delivery of multiple siRNAs with bivalent aptamer represents a novel approach for targeted combination therapy.

Highlights

As nucleic acid-based molecules, aptamers possess significant advantages over antibodies including ease of modification, ease of production, low cost, low immunogenicity, low toxicity and small size, all of which make aptamers ideal candidates for targeted cancer therapy
Our results highlight that co-delivery of multiple siRNAs with bivalent aptamer represents a novel approach for targeting combination therapy
Cell-based systematic evolution of ligands by exponential enrichment (SELEX) allows the selection of internalized aptamer, which can introduce the intracellular delivery of cargo through receptor-mediated endocytosis [8, 9]

Summary

Introduction

As nucleic acid-based molecules, aptamers possess significant advantages over antibodies including ease of modification, ease of production, low cost, low immunogenicity, low toxicity and small size, all of which make aptamers ideal candidates for targeted cancer therapy. The selective delivery of siRNAs in a cell type-specific manner represents the major challenge for the application of RNA interference for disease treatment. Novel bivalent aptamer-dual siRNA chimera (PSMA aptamer- survivin siRNA -EGFR siRNA -PSMA aptamer, PSEP) was developed by fusing two siRNAs (specific to EGFR and survivin) between two PSMA aptamers.

Results

Conclusion