mRNA-therapy: problems and prospects of application in nephrology

The successful application of messenger RNA (mRNA)-based vaccines for the prevention of COVID-19 infection has drawn the attention of the scientific community to the potential clinical applications of these molecules as innovative and alternative therapeutic approaches in various fields of medicine. As therapeutic agents, mRNAs may be advantageous due to their unique biological properties – the ability to target virtually any genetic component of the cell and encode any proteins and peptides without the need to transfer them to the nuclei of target cells. In addition, these molecules can be rapidly designed/produced and clinically tested. Once the RNA chemistry and delivery system are optimized, the cost of developing new variants of these drugs for newly selected clinical diseases is greatly reduced. However, despite their potential value as novel therapeutic weapons against several kidney diseases, the complex kidney architecture and the inability of oligonucleotide-containing nanoparticles to cross the integral glomerular filtration barrier have greatly reduced their potential application in nephrology. Nevertheless, technical improvements in mRNAs that increase translation efficiency, modulate innate and adaptive immunogenicity, and improve their selective delivery to the site of action are expected to overcome these limitations and the potential for kidneytargeted therapies will greatly expand over the next few years. This is all the more important given that chronic kidney disease (CKD) affects just over 10 % of the world's adult population to some degree, and CKD is projected to become the fifth leading cause of death by 2040, with about half of patients dying from cardiovascular disease. The purpose of this mini-review is to provide a summary of the main benefits of RNAi-based therapies and illustrate the potential future directions and challenges of this promising technology for widespread therapeutic use in nephrology.

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