Templated synthesis of spherical RNA nanoparticles with gene silencing activity

Abstract

RNA has inherent therapeutic and structural properties that make it an important component of biologically-functional nanoparticles. Using DNA-amphiphiles as synthetic templates, we report the synthesis of two classes of RNA-amphiphiles that self-assemble into spherical nanoparticles in aqueous solution and show gene silencing activity.

Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)

“…In order to provide evidence of gene knockdown at the RNA level, we targeted the APOB gene in HepG2 cells. 35 We quantified the relative silencing by measuring mRNA degradation with RT-qPCR. The data ( Fig.…”

Hydrophobic Interaction: A Promising Driving Force for the Biomedical Applications of Nucleic Acids

“…These methods include 1) the separation is proceeded by the differences in molecular weights, such as dialysis, ultrafiltration, and electrophoresis gel, [69] 2) reversed-phase chromatography exerts separation by the polar differences, [70,71] 3) size exclusion chromatography exerts separation by the differences in molecular sizes, [72][73][74][75] and 4) anion exchange chromatography exerts separation by the charge density differences. [76] The most commonly used hydrophobic moieties ( Figure 6A-G) of DNA amphiphiles can be roughly divided into the following categories: 1) lipids (such as fatty chains, cholesterol, and their analogs), [77][78][79][80] 2) -conjugated molecules (including hydrophobic fluorescent dyes and conjugated polymers), [76,81,82] 3) strongly hydrophobic polymers (polystyrene, polynorbornene (PNB) derivatives grafted with aromatic rings), [74,75] 4) biodegradable polymers ((polylactic acid (PLA), polycaprolactone (PCL), and polylactic acid-glycolic acid (PLGA)), [66,[83][84][85][86] 5) stimulus-responsive polymers ((temperature-responsive poly(Nisopropylacrylamide) (PNIMAP), [64] pH-responsive polyacrylic acid (PAA)), [87] 6) some other hydrophobic molecules ((poly phosphorylated hexaethylene (HE n ), [88] polypropylene oxide (PPO)), [89][90][91] and 7) aggregation-induced emission (AIE)-based molecules. [92,93] These hydrophobic moieties are chemically conjugated to DNAs (with different sequence lengths) through covalent bonds, producing various DNA amphiphiles.…”

Lipid–oligonucleotide conjugates for bioapplications

“…A more recent study from the Sleiman group reported two methods for conjugating specific RNA strands with hydrophobic chains, allowing the formation of RNA-amphiphiles and subsequent efficient gene-silencing capability [ 88 ]. As shown in Fig.…”

“…7 A and B, by employing dibenzocyclooctyne group (DBCO)-labeled DNA-amphiphile as a template, azide-modified RNA was directly attached to the hydrophobic chain via ‘click-chemistry’ and the hybridized DNA could then be removed by adding DNase I. This interesting method provided a novel solution to the challenge of linking RNA strands with hydrophobic molecules, and the outcome has improved the efficacy of RNA therapeutics [ 88 ]. To further increase therapeutic efficiency, another study has also reported that the co-delivery of small-molecule anticancer drugs and nucleotide molecules simultaneously could show a synergistic effect for specific tumor treatment [ 89 ].…”