RNA-DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-κB in human cells

Weina Ke, Enping Hong, Renata F. Saito, Maria Cristina Rangel, Jian Wang, Mathias Viard, Melina Richardson, Emil F. Khisamutdinov, Martin Panigaj, Nikolay V. Dokholyan, Roger Chammas, Marina A. Dobrovolskaia, Kirill A. Afonin

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Nucleic acid-based assemblies that interact with each other and further communicate with the cellularmachinery in a controlledmanner represent a new class of reconfigurable materials that can overcome limitations of traditional biochemical approaches and improve the potential therapeutic utility of nucleic acids. This notion enables the development of novel biocompatible 'smart' devices and biosensors with precisely controlled physicochemical and biological properties. We extend this novel concept by designing RNA-DNA fibers and polygons that are able to cooperate in different human cell lines and that have defined immunostimulatory properties confirmed by ex vivo experiments. The mutual intracellular interaction of constructs results in the release of a large number of different siRNAs while giving a fluorescent response and activating NF-κB decoy DNA oligonucleotides. This work expands the possibilities of nucleic acid technologies by (i) introducing very simple design principles and assembly protocols; (ii) potentially allowing for a simultaneous release of various siRNAs together with functional DNA sequences and (iii) providing controlled rates of reassociation, stabilities stabilities in human blood serum, and immunorecognition.

Original languageEnglish (US)
Pages (from-to)1350-1361
Number of pages12
JournalNucleic acids research
Volume47
Issue number3
DOIs
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • Genetics

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    Ke, W., Hong, E., Saito, R. F., Rangel, M. C., Wang, J., Viard, M., Richardson, M., Khisamutdinov, E. F., Panigaj, M., Dokholyan, N. V., Chammas, R., Dobrovolskaia, M. A., & Afonin, K. A. (2019). RNA-DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-κB in human cells. Nucleic acids research, 47(3), 1350-1361. https://doi.org/10.1093/nar/gky1215