Efficient mRNA Delivery with mRNA Lipoplexes Prepared Using a Modified Ethanol Injection Method.

Messenger RNA (mRNA)-based therapies are a novel class of therapeutics used in vaccination and protein replacement therapies for monogenic diseases. Previously, we developed a modified ethanol injection (MEI) method for small interfering RNA (siRNA) transfection, in which cationic liposome/siRNA complexes (siRNA lipoplexes) were prepared by mixing a lipid-ethanol solution with a siRNA solution. In this study, we applied the MEI method to prepare mRNA lipoplexes and evaluated the in vitro and in vivo protein expression efficiencies. We selected six cationic lipids and three neutral helper lipids to generate 18 mRNA lipoplexes. These were composed of cationic lipids, neutral helper lipids, and polyethylene glycol-cholesteryl ether (PEG-Chol). Among them, mRNA lipoplexes containing N-hexadecyl-N,N-dimethylhexadecan-1-aminium bromide (DC-1-16) or 11-((1,3-bis(dodecanoyloxy)-2-((dodecanoyloxy)methyl) propan-2-yl) amino)-N,N,N-trimethyl-11-oxoundecan-1-aminium bromide (TC-1-12) with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and PEG-Chol exhibited high protein expression in cells. Furthermore, mRNA lipoplexes composed of DC-1-16, DOPE, and PEG-Chol exhibited high protein expression in the lungs and spleen of mice after systemic injection and induced high antigen-specific IgG1 levels upon immunization. These results suggest that the MEI method can potentially increase the efficiency of mRNA transfection, both in vitro and in vivo.

Air-permeable redox mediated transcutaneous CO2 sensor.

Standard clinical care of neonates and the ventilation status of human patients affected with coronavirus disease involves continuous CO2 monitoring. However, existing noninvasive methods are inadequate owing to the rigidity of hard-wired devices, insubstantial gas permeability and high operating temperature. Here, we report a cost-effective transcutaneous CO2 sensing device comprising elastomeric sponges impregnated with oxidized single-walled carbon nanotubes (oxSWCNTs)-based composites. The proposed device features a highly selective CO2 sensing response (detection limit 155 ± 15 ppb), excellent permeability and reliability under a large deformation. A follow-up prospective study not only offers measurement equivalency to existing clinical standards of CO2 monitoring but also provides important additional features. This new modality allowed for skin-to-skin care in neonates and room-temperature CO2 monitoring as compared with clinical standard monitoring system operating at high temperature to substantially enhance the quality for futuristic applications.