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
Title | Year | Author | Number |
---|---|---|---|
COMPOSITIONS AND METHODS FOR TREATING HAEMOGLOBINOPATHIES | 2015 |
|
RU2707540C2 |
COMPOSITIONS AND METHODS OF TREATING HEMOGLOBINOPATHIES | 2016 |
|
RU2812491C2 |
IMMUNOLOGICALLY DISTINCT CELL SURFACE VARIANTS FOR CELL THERAPY APPLICATIONS | 2017 |
|
RU2793803C2 |
COMPOSITIONS INCREASING THE NUMBER OF COPIES OF THE VECTOR (VCN), AND METHODS OF USING | 2017 |
|
RU2744603C2 |
CELL TARGETING MEDIATED BY CHIMERIC ANTIGEN RECEPTOR | 2018 |
|
RU2783316C2 |
RNA-guided destruction of human JC virus and other poliomaviruses | 2015 |
|
RU2747722C2 |
METHOD FOR CREATION OF T-CELLS SUITABLE FOR ALLOGENEIC TRANSPLANTATION | 2015 |
|
RU2752933C2 |
TAU MODULATORS AND METHODS AND COMPOSITIONS FOR THEIR DELIVERY | 2017 |
|
RU2789459C2 |
GENE EDITING USING MODIFIED CLOSED-END DNA (ceDNA) | 2018 |
|
RU2811724C2 |
CRISPR ENZYME MUTATIONS REDUCING NON-TARGETED EFFECTS | 2016 |
|
RU2752834C2 |
Authors
Dates
2018-04-17—Published
2013-02-22—Filed