title: Selective delivery of therapeutic single strand antimiRs by aptamer-based conjugates.
abstract: Development of RNA-based antagonists (antimiRs) for disease-associated miRNAs in specific cell types or tissues has recently become a promising approach for treating several pathological conditions, including cancer. In order to explore the use of RNA-aptamers as carriers for cell-targeted delivery of antimiRs, here we designed two different conjugates using as carrier two aptamers that bind and antagonize cancer-associated receptor tyrosine kinases, Axl and PDGFRβ. We conjugated the tumor suppressor antimiR-222 to each aptamer demonstrating: 1) effective and selective delivery to receptor-expressing tumor cells, 2) increased expression of miR-222 target mRNAs, and 3) functional synergy between the kinase inhibitory aptamer and the antimiR antagonizing functions. Furthermore, we generated modular molecules in which two different antimiR sequences connected in tandem are conjugated to a unique carrier aptamer. We proved this strategy to be effective to deplete multiple microRNAs simultaneously, thus combining the effects of different antimiRs without losing the cell targeting specificity.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Naples, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Catuogno
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rienzo
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Naples, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Di Vito
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Naples, Italy.
authors.forename: Carla Lucia
authors.initials: CL
authors.lastname: Esposito
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Naples, Italy. Electronic address: defranci@unina.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: de Franciscis
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D052157:Aptamers, Nucleotide; D015850:Interleukin-6; D016209:Interleukin-8; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C577686:interleukin-6, mouse; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D015088:2',5'-Oligoadenylate Synthetase; D000094963:Axl Receptor Tyrosine Kinase
keywords: AntimiR; Aptamer; Cancer; Targeted delivery; Therapy