title: An aptamer-siRNA chimera silences the eukaryotic elongation factor 2 gene and induces apoptosis in cancers expressing αvβ3 integrin.
abstract: 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 (αvβ3) 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 αvβ3 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.
authors.affiliation: Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, Helmholtz-Institute for Biomedical Engineering, Aachen, Germany.
authors.forename: Ahmad Fawzi
authors.initials: AF
authors.lastname: Hussain
authors.forename: Mehmet Kemal
authors.initials: MK
authors.lastname: Tur
authors.forename: Stefan
authors.initials: S
authors.lastname: Barth
mesh_terms: D017209:Apoptosis; D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020652:Peptide Elongation Factor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*
chemical_list: D052157:Aptamers, Nucleotide; D039302:Integrin alphaVbeta3; D020652:Peptide Elongation Factor 2; D034741:RNA, Small Interfering