Recombinant virus expressing tpk and use thereof in treatment of alzheimer's disease
OwnerJingjing WANG, Shaoming SANG +1inventors
InventorsJingjing WANG, Shaoming SANG, Huan ZHANG
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Abstract
Provided is a recombinant adeno-associated virus (rAAV) or recombinant lentivirus, comprising an expression cassette in the genome, the expression cassette comprises a polynucleotide encoding thiamine pyrophosphokinase (TPK), which is operatively linked to a promoter. Also provided are also a pharmaceutical composition comprising the rAAV or recombinant lentivirus, and use of the rAAV, recombinant lentivirus and the pharmaceutical composition in the preparation of a medicament for treating or preventing Alzheimer's disease.
Claims33
A recombinant adeno-associated virus (rAAV) or recombinant lentivirus, comprising in the genome an expression cassette comprising a polynucleotide encoding thiamine pyrophosphokinase (TPK) operatively linked to a promoter.
A modified thiamine pyrophosphokinase (TPK) polypeptide, comprising, as compared to an initial TPK polypeptide, the substitution of amino acid at one or more positions selected from the group consisting of positions 13, 30, 31, 37, 85, 129, 158, 181, 11 and 35, wherein the amino acid at position 13 is substituted with P, the amino acid at position 30 is substituted with A, the amino acid at position 31 is substituted with R, the amino acid at position 37 is substituted with K, the amino acid at position 85 is substituted with K, the amino acid at position 129 is substituted with G, the amino acid at position 158 is substituted with K, the amino acid at position 181 is substituted with S, the amino acid at position 11 is substituted with W, the amino acid at position 35 is substituted with W,
- wherein the modified TPK polypeptide has an improved catalytic activity of converting thiamine (TM) to thiamine diphosphate (TDP) as compared to the initial TPK polypeptide, and
- wherein the positions are numbered by reference to SEQ ID NO:
- 1 or 8.
Dependencies are inferred from the claim text.