Anti-ghrelin butyrylcholinesterase enzyme therapeutic
OwnerMatthew Nealinventor
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Abstract
Compositions and methods are provided for inactivating ghrelin in mammalian cells by administration of a polynucleotide encoding a butyrylcholinesterase (BChE) enzyme.
Claims18
A recombinant polynucleotide that expresses a butyrylcholinesterase (BChE) enzyme that inactivates the signaling hormone ghrelin, the polynucleotide comprising
- a first nucleic acid sequence that encodes a butyrylcholinesterase (BChE) enzyme, said enzyme comprising the amino acid sequence of SEQ ID NO:
- 4 or SEQ ID NO:
- 6, or the amino acid sequence of SEQ ID NO:
- 5 modified to comprise one or more amino acid substitutions selected from G117H, Y282N, G283H, T284M, and P285L or any combinations thereof, and one or more amino acid substitutions selected from A199S, S226A, S287G, A328W, F329M, and Y332G or any combination thereof.
A method of suppressing drug seeking behavior in a mammal, the method comprising administering to the mammal a composition comprising a polynucleotide that encodes a polypeptide selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 4, SEQ ID NO:
- 6 and a polypeptide of SEQ ID NO:
- 5 modified to comprise one or more amino acid substitutions selected from G117H, Y282N, G283H, T284M, and P285L, and one or more amino acid substitutions selected from A199S, S226A, S287G, A328W, F329M, and Y332G, wherein said polynucleotide is operably linked to a promoter that functions in mammalian cells;
- and a delivery vehicle, wherein the delivery vehicle is associated with said polynucleotide;
- and
- a pharmaceutically acceptable carrier.
A method of inactivating ghrelin, the method comprising the step of contacting n-octanyl acylated ghrelin with an effective amount of a BChE enzyme to cleave the n-ocanoyl group and therefore inactivating ghrelin, wherein the BChE enzyme comprises polypeptide of SEQ ID NO:
- 6 or a polypeptide of SEQ ID NO:
- 5, wherein the sequence of SEQ ID NO:
- 5 is modified to comprise one or more amino acid substitutions selected from G117H, Y282N, G283H, T284M, and P285L, and one or more amino acid substitutions selected from A199S, S226A, S287G, A328W, F329M, and Y332G.
Dependencies are inferred from the claim text.