Introducing mRNA in human macrophages with high efficiency and few side effects
Different paths to protein expression upon cells' transfection with mRNA or pDNA. Source: https://www.nature.com/articles/s41598-020-60506-4
The introduction of nucleic acids into cells, or ‘transfection’, is a methodological basis of genetic engineering. In most cases, DNA is transfected (e.g. with circular pieces of DNA called plasmids), and is then transcribed into messenger RNA (mRNA), which is then in turn translated into proteins. New technologies for the synthesis of mRNA can instead, however, be used to enable non-permanent, highly efficient and safer genetic interventions in cells in biomedical applications compared to DNA.
Hanieh Moradian, doctoral student at the Institute of Biomaterial Science and first author of the study. Photo: Hamidreza Fasehee
In this study, published today in Scientific Reports, mRNAs were synthesized with differently chemically modified nucleosides, packaged into nanoparticles with different carrier systems (lipids, polymers) and transfected into human macrophages. Macrophages are a cell type essential for innate immune defence, and control the body's response to implanted biomaterials. However, they too have defence mechanisms against "attack" by foreign nucleic acids, mostly of viral origin.
In this study, conditions were established under which the natural defence mechanisms of macrophages against foreign mRNA were hardly stimulated, even at high transfection efficiency - a prerequisite for use in biomedical research and translation.
- RNA Transfection-Induced Activation of Primary Human Monocytes and Macrophages: Dependence on Carrier System and Nucleotide Modification Moradian, H., Roch, T., Lendlein, A., Gossen, M.; Sci Rep 10, 4181 (2020). https://doi.org/10.1038/s41598-020-60506-4