An Anti-BCMA RNA Aptamer for miRNA Intracellular Delivery

Silvia Catuogno, Maria Teresa Di Martino, Silvia Nuzzo, Carla Lucia Esposito, Pierfrancesco Tassone, Vittorio de Franciscis

Research output: Contribution to journalArticle

Abstract

B cell maturation antigen is highly expressed on malignant plasma cells in human multiple myeloma and has recently emerged as a very promising target for therapeutic interventions. Nucleic-acid-based aptamers are small oligonucleotides with high selective targeting properties and functional advantages over monoclonal antibodies, as both diagnostic and therapeutic tools. Here, we describe the generation of the first-ever-described nuclease resistant RNA aptamer selectively binding to B cell maturation antigen. We adopted a modified cell-based systematic evolution of ligands by exponential enrichment approach allowing the enrichment for internalizing aptamers. The selected 2′Fluoro-Pyrimidine modified aptamer, named apt69.T, effectively and selectively bound B cell maturation antigen-expressing myeloma cells with rapid and efficient internalization. Interestingly, apt69.T inhibited APRIL-dependent nuclear factor κB (NF-κB) pathway in vitro. Moreover, the aptamer was conjugated to microRNA-137 (miR-137) and anti-miR-222, demonstrating high potential against tumor cells. In conclusion, apt69.T is a novel tool suitable for direct targeting and delivery of therapeutics to B cell maturation antigen-expressing myeloma cells.

Original languageEnglish
Pages (from-to)981-990
Number of pages10
JournalMolecular Therapy - Nucleic Acids
Volume18
DOIs
Publication statusPublished - Dec 6 2019

Keywords

  • aptamer-based conjugates
  • aptamers
  • BCMA
  • cell-internalizing SELEX
  • multiple myeloma
  • targeted delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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  • Cite this

    Catuogno, S., Di Martino, M. T., Nuzzo, S., Esposito, C. L., Tassone, P., & de Franciscis, V. (2019). An Anti-BCMA RNA Aptamer for miRNA Intracellular Delivery. Molecular Therapy - Nucleic Acids, 18, 981-990. https://doi.org/10.1016/j.omtn.2019.10.021