Gene Therapy Drugs Based on Synthetic Oligonucleotides

Abstract

The development of drugs which structure resembles or is completely identical to the natural components of a living organism is currently a promising area that is of great interest for scientists. Obtaining synthetic analogs of nucleic acids was made possible due to the active development of oligonucleotide synthesis in the 1980s and subsequent research in the field of chemical modification of nucleotides, which allowed to change the properties of nucleic acids and increase their stability. The accumulated worldwide experience has made it possible to create drugs based on synthetic oligonucleotides aimed at the treatment of rare genetic diseases. Since 1998, a relatively small number of drugs have been approved by regulatory authorities in different countries for use in clinical practice. Most of them are aimed at the treatment of orphan diseases. To date, there are 20 therapeutic drugs based on synthetic oligonucleotides that have been approved by medical regulatory authorities for use in clinical practice. Of this list, only one drug was developed in Russia (MIR 19^®). This review describes all drugs based on synthetic oligonucleotides approved up to 2024, and also examines and systematizes current knowledge about promising types of therapeutic oligonucleotides with different mechanisms of interaction with the target.