NOVEL METHODS OF PRODUCING OLIGONUCLEOTIDES Russian patent published in 2020 - IPC C07H1/00 C07H21/00 C12N9/00 

FIELD: chemistry.

SUBSTANCE: invention relates to methods of producing oligonucleotide products which can be used in pharmaceutical industry. Disclosed is a method of producing a single-stranded oligonucleotide product with length of 10 to 200 nucleotides, having at least one nucleotide residue, modified in position 2' saccharide group, nucleotide base or frame, in gram, or kilogram, or larger scale, and/or in reactor with volume of 1 l or more, where oligonucleotide matrix (I) is used, complementary to product sequence, where matrix is attached to carrier material; oligonucleotide pool (II) is used, which are segments of the product sequence with length from 3 to 15 nucleotides, where at least one segment contains at least one above modified nucleotide residue; bringing into contact (I) and (II) under conditions providing annealing; oligonucleotide segments are joined by enzymatic ligation using ligase to form a product; conditions are changed for separation of any impurities, including denaturation of hybridized matrix and impurity oligonucleotide chains and impurities are separated; conditions for separation of the product are changed, including denaturation of the hybridized matrix and chains of the oligonucleotide product and the product is separated; and subjected to processing matrix for use in future reactions. Also disclosed is a method of producing a double-stranded oligonucleotide product, where 2 complementary single-stranded oligonucleotides are obtained by the above method and then mixed under conditions providing annealing.

EFFECT: novel efficient methods of producing oligonucleotide products, which enable to obtain oligonucleotides in large quantities.

17 cl, 17 dwg, 24 tbl, 14 ex