OLIGONUCLEOTIDE COMPOSITIONS AND METHODS RELATED TO THEM Russian patent published in 2023 - IPC C07C317/28 C07D295/88 C12N15/11 C12N15/113 C12Q1/68 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a composition of oligonucleotides capable of mediating dystrophin exon skipping, to a pharmaceutical composition containing this composition, and to a method for altering the splicing of a target transcript using this composition. The proposed composition contains an effective amount of oligonucleotides of a certain type of oligonucleotides, determined by the following: 1) the sequence of bases; 2) core bond profile; 3) the profile of the chiral centers of the backbone; and 4) profile of backbone phosphorus modifications. In this case, the composition is characterized by controlled chirality due to its being enriched, relative to the essentially racemic preparation of oligonucleotides having the same base sequence, with oligonucleotides of a certain type of oligonucleotides. Moreover: oligonucleotides of a certain type of oligonucleotides are structurally identical; oligonucleotides of a certain type of oligonucleotides are characterized by a common stereochemical configuration of 5 or more chiral internucleotide bonds, each of which is independently an Rp or Sp configuration; each of the oligonucleotides of a certain type of oligonucleotide contains 3 or more consecutive 2'-F modified sugar moiety; and at least 50% of the phosphorothioate internucleotide bonds of an oligonucleotide of a certain type of oligonucleotides are characterized by the Sp conformation.

EFFECT: development of new and improved antisense oligonucleotides and miRNA oligonucleotides and compositions of oligonucleotides.

33 cl, 38 dwg, 19 ex