NOVEL VIRAL VECTOR CONSTRUCT FOR NEURON SPECIFIC CONTINUOUS DOPA SYNTHESIS IN VIVO Russian patent published in 2017 - IPC A61K48/00 C12N15/864 A61P25/16 

FIELD: medicine.

SUBSTANCE: inventions relate to dicistronic expression vector, its application for amelioration of Parkinson's disease, pharmaceutical composition and a method for determining the expression ratio of polypeptide of GTP-cyclohydrolase 1 and polypeptide of tyrosine hydroxylase expressed by said dicistronic vector. Presented vector contains the first top expression cassette along the transcription and the second lower expression cassette along the transcription. Said first top expression cassette along the transcription contains nucleotide sequence containing the first promoter sequence functionally connected with the first nucleotide sequence, wherein said first nucleotide sequence encodes GTP-cyclohydrolase 1 polypeptide (GCH1; EC 3.5.4.16). Said second lower expression cassette along the transcription contains nucleotide sequence containing the second promoter sequence functionally connected with the second nucleotide sequence. Said second nucleotide sequence encodes tyrosine hydroxylase polypeptide (TH; EC 1.14.16.2). At that, the vector is adeno-associated vector (AAV) and said second nucleotide sequence is functionally related to woodchuck posttranscriptional regulatory element (WPRE). Said first and second promoters are promoters of synapsin 1, the first top expression cassette along the transcription and second lower expression cassette along the transcription contain polyadenylation sequence, and expression cassettes of the dicistronic expression vector contain 5'-end repeated sequence and 3'-end repeated sequence. Polypeptides of tyrosine hydroxylase and GTP-cyclohydrolase 1 can be expressed in ratio from 3:1 to 7:1, respectively. Inventions can be used for recovery of catecholamine balance in a subject in need thereof.

EFFECT: present invention is applicable for treating disorders associated with dopamine deficiency.

21 cl, 8 dwg, 1 tbl, 3 ex