Bacteria engineered to treat diseases associated with hyperammonemia
AssigneeSynlogic, Inc.
InventorsDean Falb, Vincent M. Isabella, Jonathan W. Kotula, Paul F. Miller, Suman Machinani
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Abstract
Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of modulating and treating disorders associated with hyperammonemia are disclosed.
Claims20
A bacterium comprising a gene sequence encoding an arginine feedback resistant N-acetylglutamate synthetase (ArgAfbr), wherein the ArgAfbr has reduced arginine feedback inhibition as compared to a wild-type N-acetylglutamate synthetase from the same bacterial subtype under the same conditions,
- wherein the gene sequence encoding the ArgAfbr is present in the bacterial chromosome and is operably linked in the chromosome to a promoter that is induced by low-oxygen or anaerobic conditions;
- wherein the bacterium has been modified to lack a functional ArgR;
- and
- wherein the bacterium is an auxotroph in a gene that is complemented when the bacterium is present in a mammalian gut.
A bacterium comprising a gene sequence encoding an arginine feedback resistant N-acetylglutamate synthetase (ArgAfbr), wherein the ArgAfbr has reduced arginine feedback inhibition as compared to a wild-type N-acetylglutamate synthetase from the same bacterial subtype under the same conditions,
- wherein the gene sequence encoding the ArgAfbr is operably linked to a promoter that is induced by low-oxygen or anaerobic conditions;
- wherein the bacterium has been modified to lack a functional ArgR;
- and
- wherein the bacterium comprises a gene sequence encoding a biosynthetic pathway for producing butyrate.
Dependencies are inferred from the claim text.