RNA–DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-κB in human cells
Year: 2018
Type: article
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-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 in human blood serum, and immunorecognition.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gky1215
Institutions: University of North Carolina at Charlotte, Frederick National Laboratory for Cancer Research, National Cancer Institute, Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, Pennsylvania State University, Leidos Biomedical Research Inc. (United States), Ball State University, University of Pavol Jozef Šafárik
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Awards: The use if RNA-based nano formulations to improve the efficacy of breast cancer treatment and reduce therapy-induced cardiotoxicity, REU Site: Nanoscale Science Undergraduate Research Experience (NanoSURE) at UNC Charlotte, REU Site: Nanoscale Science Undergraduate Research Experience (NanoSURE) at UNC Charlotte, G3503792436, G386607036, Genome-Scale Analysis of RNA Virus Tertiary Structure, Integrating cheminformatics and molecular simulations for virtual drug screening, G5888954722, G6055273096, Engineering allostery for in vivo protein control, Cancer and heart: new paradigms of diagnosis and treatment, Characterization of various multifunctional nucleic acid nanoparticles and understanding their immunotoxicity
OpenAlex ID: W2903116424