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AssigneeSynlogic Operating Company, Inc.
InventorsVincent M. Isabella, Sean Cotton
Estimating the term…
The present disclosure provides recombinant bacterial cells that have been engineered with genetic circuitry which allow the recombinant bacterial cells to sense a patient's internal environment and respond by turning an engineered metabolic pathway on or off. When turned on, the recombinant bacterial cells complete all of the steps in a metabolic pathway to achieve a therapeutic effect in a host subject. These recombinant bacterial cells are designed to drive therapeutic effects throughout the body of a host from a point of origin of the microbiome. Specifically, the present disclosure provides recombinant bacterial cells that comprise an amino acid catabolism enzyme, e.g., a methionine catabolism enzyme for the treatment of diseases and disorders associated with amino acid metabolism, including homocystinuria, in a subject. The disclosure further provides pharmaceutical compositions and methods of treating disorders associated with amino acid metabolism, such as homocystinuria.
A recombinant bacterial cell comprising a heterologous gene sequence encoding a methionine catabolism enzyme operably linked to a first promoter that is not associated with the gene encoding the amino acid catabolism enzyme in nature.
The recombinant bacterial cell of any one of the previous claims, further comprising genetic modification that reduces export of methionine from the bacterial cell.
The recombinant bacterial cell of any one of the previous claims, further comprising a heterologous gene encoding a methionine importer.
The recombinant bacterial cell of any one of the previous claims, further comprising a second heterologous gene sequence encoding a second methionine catabolism enzyme operably linked to the first promoter that is not associated with the gene encoding the second methionine catabolism enzyme in nature.
The recombinant bacterial cell of any one of the previous claims, wherein the first promoter is an inducible promoter.
The recombinant bacterial cell of any one of the previous claims, wherein the heterologous gene encoding the methionine catabolism enzyme is located on a plasmid or a chromosome in the bacterial cell.
The recombinant bacterial cell of any one of the previous claims, wherein the recombinant bacterial cell is a recombinant probiotic bacterial cell.
The recombinant bacterial cell of any one of the previous claims, wherein the recombinant bacterial cell is an auxotroph in a gene that is complemented when the recombinant bacterial cell is present in a mammalian gut.
The recombinant bacterial cell of any one of the previous claims, wherein the recombinant bacterial cell has a methionine degradation activity of about 0.1 μmol/hr/1×109 cells to about 1.5 μmol/hr/1×109 cells.
A pharmaceutical composition comprising the recombinant bacterial cell of any one of the previous claims and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.