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In contrast to vaccine approaches, gene therapy is primarily used for the delivery of therapeutic transgenes into the nucleus of target cells that lack a nucleus, such as T-cells, which are transiently activated by mRNA in vitro or in vivo. In DC vaccines, mRNA is transfected ex vivo and introduced into the endoplasmic reticulum (ER) of DCs. In APC-targeted vaccines, mRNA is transfected in situ to target mRNAs for translation into proteins in APCs. The transfection of mRNA leads to death of the majority of the transfected cells. It has been hypothesised that regenerating cells can take up the mRNA and translate it in the new location, introducing tumor antigens or the transgene encoding the therapeutic protein to APCs. To achieve efficient protein expression, introduction of mRNA needs transfection reagents that cross-link with mRNA in the cytosol of the target cells. These reagents are commonly polymers like protamine, poly(A)+tail or the cationic lipids DOTAP or lipofectamine. A recent study showed that gene therapy with mRNA encoding the reporter gene firefly luciferase under the control of the CMV promoter and the poly(A) tail derived from the SV40 late gene downstream of a second CMV promoter significantly increased tumor cell killing and DC stimulation in vitro compared to standard mRNA delivery.
We use messenger RNA (mRNA) to entrain vaccine. In other words, mRNA is used to induce a vaccine. This requires translating mRNA into proteins in the cytosol. This process also kills the majority of cells that were previously transfected. Usually, mRNAs are encased into lipids, polymers or microparticles. Thereby, we can control the protein expression time and location. In recent decades, several mRNA-based vaccines have been developed or are currently under development for the treatment of cancer. The Vaccine of the Year 2014 is a novel nanoparticle-encapsulated mRNA vaccine, also known as mRNA Nanoparticle-based mRNA vaccine (mRNA nanoparticle vaccine) or mRNA vaccine. d2c66b5586
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