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

Author(s):Show less -

Ke, Weina ^[1] ; Hong, Enping ^[2] ; Saito, Renata F. ^{[3, 4]} ; Rangel, Maria Cristina ^{[3, 4]} ; Wang, Jian ^[5] ; Viard, Mathias ^[6] ; Richardson, Melina ^[1] ; Khisamutdinov, Emil F. ^[7] ; Panigaj, Martin ^[8] ; Dokholyan, V, Nikolay ; Chammas, Roger ^{[3, 1, 4]} ; Dobrovolskaia, Marina A. ^[2] ; Afonin, Kirill A. ^{[1, 9]}

Affiliation

^[1] Univ North Carolina Charlotte, Dept Chem, Nanoscale Sci Program, Charlotte, NC 28223 - USA

^[2] NCI, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 - USA

^[3] Inst Canc Estado Sao Paulo, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, Ctr Invest Translac Oncol LIM24, Sao Paulo, SP - Brazil

^[5] V, Penn State Coll Med, Dept Biochem & Mol Biol, Dept Pharmacol, Hershey, PA 17033 - USA

^[6] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Basic Sci Program, Frederick, MD 21702 - USA

^[7] Ball State Univ, Dept Chem, Muncie, IN 47306 - USA

^[8] Pavol Jozef Safarik Univ Kosice, Fac Sci, Inst Biol & Ecol, Kosice - Slovakia

^[9] Univ North Carolina Charlotte, Ctr Biomed Engn & Sci, Charlotte, NC 28223 - USA

• Document type: Journal article
• Source: Nucleic Acids Research; v. 47, n. 3, p. 1350-1361, FEB 20 2019.
• Web of Science Citations: 10

Abstract

Nucleic acid-based assemblies that interact with each other and further communicate with the cellular machinery in a controlled manner 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-B 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 in human blood serum, and immunorecognition. (AU)

• FAPESP's process: 17/50029-6 - The use if RNA-based nano formulations to improve the efficacy of breast cancer treatment and reduce therapy-induced cardiotoxicity
• Grantee: Roger Chammas
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants