IP Library › Granted Patent US 12703866
Granted Patent B2
US 12703866 · App. 18/265,002 · Granted Aug 11, 2026

Engineered microorganisms

Inventors: Michael James (Cambridge, MA); Aida Kalantari (Cambridge, MA); Tea Mirabella (Cambridge, MA); Lauren Renaud (Cambridge, MA); Lee Kristensen (Cambridge, MA); Vincent Isabella (Cambridge, MA)
Assignee: Synlogic Operating Company, Inc.
C12N15/52C07K14/245C12R2001/19
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Quick Facts
Patent No.
US 12703866
App. No.
18/265,002
Granted
Aug 11, 2026
Kind
B2
Abstract

The present invention relates to engineered microorganisms, wherein the engineered microorganisms comprise a therapeutic molecule and a modified pks island.

Claims (25)

1 . An engineered bacterium comprising one or more gene(s) or gene cassette(s) encoding a therapeutic molecule and a modified pks island as compared to a corresponding bacterium comprising an unmodified pks island,

wherein the modified pks island comprises

1) a full or partial deletion of the clbA, clbB, clbC, clbD, clbE, clbF, clbG, clbH, clbI, clbJ, clbK, clbL, clbM, clbN, clbO, clbP, clbQ, and clbR gene sequences; and

2) an intact or unmodified clbS gene sequence; and

3) a full or partial deletion of the promoter operably linked to clbS;

wherein the therapeutic molecule is a protein, and

wherein the engineered bacterium is an engineered Escherichia coli.

2 . The engineered bacterium of claim 1 , wherein the therapeutic molecule is

1) a phenylalanine metabolizing enzyme; or

2) an oxalate metabolic enzyme; or

3) is a protein capable of reducing a deleterious molecule.

3 . The engineered bacterium of claim 1 , wherein the engineered bacterium is an engineered Escherichia coli Nissle.

4 . The engineered bacterium of claim 1 , wherein the engineered bacterium produces less colibactin compared to a corresponding bacterium comprising an unmodified pks island.

5 . The engineered bacterium of claim 1 , wherein the engineered bacterium produces less colibactin precursor or metabolite compared to a corresponding bacterium comprising an unmodified pks island.

6 . The engineered bacterium of claim 1 , wherein the engineered bacterium produces less N-myristoyl-D-asparagine compared to a corresponding bacterium comprising an unmodified pks island.

7 . A pharmaceutical composition comprising the engineered bacterium of claim 1 .

8 . A method of treatment comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof.

9 . A method of reducing a deleterious molecule comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof.

10 . A method of reducing oxalate comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof, wherein the therapeutic molecule is a oxalate metabolic enzyme.

11 . A method of treating hyperoxaluria (HOX) comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof, wherein the therapeutic molecule is a oxalate metabolic enzyme.

12 . A method of reducing phenylalanine comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof, wherein the therapeutic molecule is a phenylalanine metabolizing enzyme.

13 . A method of treating hyperphenylalaninemia comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof, wherein the therapeutic molecule is a phenylalanine metabolizing enzyme.

14 . A method of treating phenylketonuria (PKU) comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof, wherein the therapeutic molecule is a phenylalanine metabolizing enzyme.

15 . A method of reducing methionine levels comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof, wherein the therapeutic molecule is a phenylalanine metabolizing enzyme.

16 . A method of treating homocysteinuria comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof, wherein the therapeutic molecule is a methionine metabolizing enzyme.