An Aptamer-siRNA Chimera Silences the Eukaryotic Elongation Factor 2 Gene and Induces Apoptosis in Cancers Expressing αvβ3 Integrin

Small interfering RNAs (siRNAs) silence gene expression by triggering the sequence-specific degradation of mRNAs, but the targeted delivery of such reagents remains challenging and a significant obstacle to therapeutic applications. One promising approach is the use of RNA aptamers that bind tumor-associated antigens to achieve the delivery of siRNAs to tumor cells displaying specific antigens. Wholly RNA-based constructs are advantageous because they are inexpensive to synthesize and their immunogenicity is low. We therefore joined an aptamer-recognizing alpha V and integrin beta 3 (alpha v beta 3) integrin to a siRNA that targets eukaryotic elongation factor 2 and achieved for the first time the targeted delivery of a siRNA to tumor cells expressing alpha v beta 3 integrin, causing the inhibition of cell proliferation and the induction of apoptosis specifically in tumor cells. The impact of our results on the development of therapeutic aptamer-siRNA constructs is discussed.