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US 2023/0174926 A1Published application
Bacteria engineered to treat disorders involving the catabolism of leucine
AssigneeSynlogic Operating Company, Inc.
InventorNing Li
Life of this patent
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AssigneeSynlogic Operating Company, Inc.
InventorNing Li
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 comprising a heterologous gene encoding an improved leucine catabolism enzyme with higher activity and/or specificity for leucine. The disclosure further provides pharmaceutical compositions comprising the recombinant bacteria, and methods for treating disorders involving the catabolism of leucine using the pharmaceutical compositions disclosed herein.
A recombinant bacterium comprising
The recombinant bacterium of any one of the previous claims, wherein the bacterium comprises a genetic modification in leuE that reduces leucine export from the bacterium.
The recombinant bacterium of any one of the previous claims, wherein the bacterium comprises a genetic modification in ilvC that reduces endogenous biosynthesis of leucine in the bacterium.
The recombinant bacterium of any one of the previous claims, wherein the at least one gene sequence encoding the at least one leucine catabolism enzyme is integrated into the chromosome of the bacterium or is present on a plasmid in the bacterium.
The recombinant bacterium of any one of the previous claims, wherein the promoter is selected from the group consisting of an FNRS promoter, a Ptet promoter, a Pcmt promoter, a Pc1857 promoter, and a PBAD promoter.
The recombinant bacterium of any one of the previous claims, wherein the bacterium is a probiotic bacterium selected from the group consisting of Bacteroides, Bifidobacterium, Clostridium, Escherichia, Lactobacillus, and Lactococcus,.
A pharmaceutically acceptable composition comprising the recombinant bacterium of any one of the previous claims and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.