COMPOSITIONS AND METHODS FOR TREATMENT OF HEMOGLOBINOPATHIES Russian patent published in 2018 - IPC C12N15/52 C12N9/16 C12N9/22 A61K38/00 A61K48/00 

FIELD: biochemistry.

SUBSTANCE: present group of inventions relates to a polynucleotide encoding a variant of homing endonuclease (HE) I-OnuI, an expression vector comprising such a polynucleotide, an endonuclease polypeptide, compositions for the treatment of hemoglobinopathy and a cell containing said polynucleotide, vector, or endonuclease-polypeptide. Described polynucleotide has the sequence of SEQ ID NO: 34 with mutations corresponding to one or more amino acid substitutions selected from the group consisting of L26, R28, R30, N32, S40, E42, G44, Q46, A70, S72, S78, K80, T82, F182, N184, I186, S190, K191, Q197, V199, S201, K225, K227, D236, V238 and T240. Resulting variant of HE I-OnuI binds to the nucleotide sequence of the silencing region of fetal hemoglobin (HbF) or Bcl11a-regulated silencing region of HbF, represented in any one of SEQ ID NO: 5–12 and 40–43, and cleaves said nucleotide sequence.

EFFECT: inventions can be used to treat thalassemia, sickle cell disease and other hemoglobinopathies.

11 cl, 35 dwg, 10 ex, 8 tbl