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