Bacteria engineered to treat diseases associated with hyperammonemia

摘要

Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of modulating and treating disorders associated with hyperammonemia are disclosed.

主权项

1. A genetically engineered bacterium comprising an arginine regulon,
wherein the bacterium comprises a gene 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 and wherein expression of the gene encoding ArgAfbr is controlled by a promoter that is induced by low-oxygen or anaerobic conditions; and wherein the bacterium has been genetically engineered to lack a functional ArgR.