FIELD: chemistry.
SUBSTANCE: present invention relates to biochemistry. Method of modulating the expression of a polynucleotide of a brain-derived neurotrophic factor (BDNF) in a biological system is described. Biological system is contacted with at least one antisense oligonucleotide, a length of 10 to 30 nucleotides, wherein said at least one antisense oligonucleotide has at least 90% complementarity and specifically hybridizes to a site of 10-30 nucleotides of the natural antisense polynucleotide for the polynucleotide of BDNF. Natural antisense polynucleotide consists essentially of a sequence selected from the group consisting of nucleotides: 1-1279 in SEQ ID NO: 3, or 1-1478 in SEQ ID NO: 4, or 1-1437 in SEQ ID NO: 5, or 1-2322 in SEQ ID NO: 6, or 1-2036 in SEQ ID NO: 7, or 1-2364 in SEQ ID NO: 8, or 1-3136 in SEQ ID NO: 9, or 1-906 in SEQ ID NO: 10, or 1-992 in SEQ ID NO: 11, which leads to modulation of the expression of the polynucleotide of brain-derived neurotrophic factor (BDNF), provided that at least one antisense oligonucleotide does not have a sequence of any of SEQ ID NO: 50-55. Analogous method for upregulating the function of the polynucleotide of BDNF in a biological system is also described. Also described is an appropriate method for upregulating the function of BDNF polynucleotide in a biological system and a method for modulating the expression of a BDNF polynucleotide in cells or tissues of a patient in vivo or in vitro, including a mammal. Oligonucleotide of 10 to 30 nucleotides in length is provided having at least one modification and/or substitution, said oligonucleotide having at least 90% complementarity and specifically hybridizing to a site of 10-30 nucleotides of the natural antisense polynucleotide for BDNF polynucleotide. Natural antisense polynucleotide consists essentially of a sequence selected from the group consisting of nucleotides: 1-1279 in SEQ ID NO: 3, or 1-1478 in SEQ ID NO: 4, or 1-1437 in SEQ ID NO: 5, or 1-2322 in SEQ ID NO: 6, or 1-2036 in SEQ ID NO: 7, or 1-2364 in SEQ ID NO: 8, or 1-3136 in SEQ ID NO: 9, or 1-906 in SEQ ID NO: 10, or 1-992 in SEQ ID NO: 11, provided that the oligonucleotide does not have a sequence of any of SEQ ID NO: 50-55, wherein at least one modification selected from: at least one modified sugar residue, at least one modified internucleotic linkage, at least one modified nucleotide, and any combination thereof. In addition, said oligonucleotide is an antisense compound that hybridizes with and increases the regulation of BDNF gene expression in vivo or in vitro as compared to a standard control. Pharmaceutical composition is described for the treatment of a disease associated with at least one BDNF polynucleotide comprising at least one oligonucleotide representative specific to one or more BDNF polynucleotides and a pharmaceutically acceptable excipient.
EFFECT: method of preventing or treating a disease associated with at least one BDNF polynucleotide and/or at least one product that it encodes, comprising administering to the patient a therapeutically effective dose of at least one oligonucleotide represented.
27 cl, 9 dwg, 1 tbl, 2 ex
