Selective delivery of therapeutic single strand antimiRs by aptamer-based conjugates

S Catuogno, A Rienzo, A Di Vito, CL Esposito… - Journal of Controlled …, 2015 - Elsevier
S Catuogno, A Rienzo, A Di Vito, CL Esposito, V de Franciscis
Journal of Controlled Release, 2015Elsevier
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 …
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.
Elsevier