Variants of yeast NDI1 gene, and uses thereof in the treatment of disease associated with mitochondrial dysfunction
AssigneeThe Provost Fellows Foundation Scholars and the Other Members of Board of the College of the Hold and Undivided Trinity of Queen Elizabeth, Near Dublin Trinity College Dublin
InventorsGwyneth Jane Farrar, Sophia Millington-Ward, Naomi Chadderton, Mathew Alan Carrigan, Paul Kenna
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Abstract
An isolated nucleic acid sequence encoding the yeast NDI1 protein of SEQ ID NO: 542 or a functional variant thereof is described. The nucleic acid sequence comprises at least 50 codons which are codon optimized compared with the sequence of yeast NDI1 gene of SEQ ID NO: 1.
Claims19
An isolated nucleic acid sequence encoding an immune optimised functional variant of the yeast NDI1 protein, wherein the amino acid sequence of the variant is either
- (i) the sequence shown as SEQ ID NO:
- 542 with at least one conservative amino acid change to a residue selected from the group consisting of:
- K284, S143, L502, L403, A387, S86, L19, K214, K373, K511, L159, R479, L483, I82, F90, L89, V266, L481, L202, L259, L150, R85, Y151, Y482, S488, V45, S80, and K196, and with no amino acid changes to residues other than the residues of said group and with no amino acid change other than a conservative amino acid change to said residues of said group, wherein a conservative amino acid change is a change for which the change in BLOSUM score is 4 or less or
- (ii) the sequence shown as residues 28 to 513 of SEQ ID NO:
- 542 with at least one conservative amino acid change to a residue selected from the group consisting of:
- K284, S143, L502, L403, A387, S86, K214, K373, K511, L159, R479, L483, I82, F90, L89, V266, L481, L202, L259, L150, R85, Y151, Y482, S488, V45, S80, and K196, and with no amino acid changes to residues other than the residues of said group and with no amino acid change other than a conservative amino acid change to said residues of said group;
- wherein a conservative amino acid change is a change for which the change in BLOSUM score is 4 or less.
An isolated nucleic add sequence encoding a functional variant of the yeast NDI1 protein of SEQ ID NO:
- 542, wherein said functional variant has at least 99% sequence identity with the polypeptide sequence corresponding to amino add residues 28 to 513 of SEQ ID NO:
- 542, wherein the nucleic add comprises 50-329 codons which are codon optimised compared with the sequence of wild-type yeast NDI1 gene of SEQ ID NO:
- 1,
- wherein said functional variant, when compared to the sequence of the polypeptide sequence corresponding to amino acid residues 28 to 513 of SEQ ID NO:
- 542, comprises at least one conservative amino acid change to a residue selected from the group consisting of:
- K284, S143, L502, L403, A387, S86, K214, K373 K511, R479, L483, 182, F90, L89 V266, L481, L202, R85, Y151, Y482, S488, V45, S80, and K196.
Dependencies are inferred from the claim text.