US 11,254,918 B2Granted

Compositions and methods for modulating growth of a genetically modified gut bacterial cell

AssigneesThe Board of Trustees of the Leland Stanford Junior University, Novome Biotechnolooies, Inc.

InventorsJustin L. Sonnenburg, Weston R. Whitaker, Elizabeth Stanley, William C. DeLoache

Life of this patent

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Abstract

Compositions and methods are provided for modulating growth of a genetically modified bacterial cell present in a human organ, for modulating growth of a genetically modified bacterial cell in an organ (e.g., gut), for displacing at least a portion of a population of bacterial cells in an organ, and for facilitating gut colonization by a genetically modified bacterial cell. Also provided are genetically modified bacterial cells, e.g., cells that include a heterologous carbohydrate-utilization gene or gene set that provides for the ability to utilize as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiome.

Claims20

Dependent claims

A method of colonizing the gut of a subject with a genetically modified, non-naturally occurring Bacteroides cell, the method comprising administering to the subject both:

a) the genetically modified Bacteroides cell, wherein the genetically modified Bacteroides cell comprises a heterologous carbohydrate-utilization gene set that provides the genetically modified Bacteroides cell with an ability to utilize as a carbon source a porphyran and the heterologous carbohydrate-utilization gene set comprises one or more nucleic acids, wherein said one or more nucleic acids encodes all of the following proteins:
a protein that has 80% or more sequence identity to SEQ ID NO:
14, a protein that has 80% or more sequence identity to SEQ ID NO:
15, a protein that has 80% or more sequence identity to SEQ ID NO:
16, a protein that has 80% or more sequence identity to SEQ ID NO:
17, a protein that has 80% or more sequence identity to SEQ ID NO:
18, a protein that has 80% or more sequence identity to SEQ ID NO:
19, a protein that has 80% or more sequence identity to SEQ ID NO:
20, a protein that has 80% or more sequence identity to SEQ ID NO:
21, a protein that has 80% or more sequence identity to SEQ ID NO:
22, a protein that has 80% or more sequence identity to SEQ ID NO:
23, a protein that has 80% or more sequence identity to SEQ ID NO:
24, a protein that has 80% or more sequence identity to SEQ ID NO:
25, a protein that has 80% or more sequence identity to SEQ ID NO:
26, a protein that has 80% or more sequence identity to SEQ ID NO:
27, a protein that has 80% or more sequence identity to SEQ ID NO:
28, a protein that has 80% or more sequence identity to SEQ ID NO:
29, a protein that has 80% or more sequence identity to SEQ ID NO:
30, a protein that has 80% or more sequence identity to SEQ ID NO:
31, a protein that has 80% or more sequence identity to SEQ ID NO:
32, a protein that has 80% or more sequence identity to SEQ ID NO:
33, and a protein that has 80% or more sequence identity to SEQ ID NO:
34;
and
b) porphyran;
wherein the genetically modified Bacteroides cell reaches an abundance of at least 107 cells/mL in the feces of the subject.

23 more elements

A method of colonizing the gut of a subject with a genetically modified, non-naturally occurring Bacteroides cell, the method comprising orally administering to the subject both:

a) the genetically modified Bacteroides cell, wherein the genetically modified Bacteroides cell comprises a heterologous carbohydrate-utilization gene set that (i) provides the genetically modified Bacteroides cell with an ability to utilize as a carbon source a porphyran, (ii) is at least 40 kb, (iii) is encoded on a plasmid, encoded on a bacterial artificial chromosome, or artificially genomically integrated, and (iv) comprises one or more nucleic acids, wherein said one or more nucleic acids encodes all of the following proteins:
a protein that has 80% or more sequence identity to SEQ ID NO:
14, a protein that has 80% or more sequence identity to SEQ ID NO:
15, a protein that has 80% or more sequence identity to SEQ ID NO:
16, a protein that has 80% or more sequence identity to SEQ ID NO:
17, a protein that has 80% or more sequence identity to SEQ ID NO:
18, a protein that has 80% or more sequence identity to SEQ ID NO:
19, a protein that has 80% or more sequence identity to SEQ ID NO:
20, a protein that has 80% or more sequence identity to SEQ ID NO:
21, a protein that has 80% or more sequence identity to SEQ ID NO:
22, a protein that has 80% or more sequence identity to SEQ ID NO:
23, a protein that has 80% or more sequence identity to SEQ ID NO:
24, a protein that has 80% or more sequence identity to SEQ ID NO:
25, a protein that has 80% or more sequence identity to SEQ ID NO:
26, a protein that has 80% or more sequence identity to SEQ ID NO:
27, a protein that has 80% or more sequence identity to SEQ ID NO:
28, a protein that has 80% or more sequence identity to SEQ ID NO:
29, a protein that has 80% or more sequence identity to SEQ ID NO:
30, a protein that has 80% or more sequence identity to SEQ ID NO:
31, a protein that has 80% or more sequence identity to SEQ ID NO:
32, a protein that has 80% or more sequence identity to SEQ ID NO:
33, and a protein that has 80% or more sequence identity to SEQ ID NO:
34;
and
b) porphyran;
wherein the genetically modified Bacteroides cell reaches an abundance of at least 107 cells/mL in the feces of the subject.

23 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/091,931Filed 6 Nov 2020 · continuation
Priority: 15 Dec 2016
Published: US 2021/0054356 A125 Feb 2021
Granted: 22 Feb 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C12N 9/2402
Acting on glycosyl compounds: hydrolysing O- and S- glycosyl compounds
A61K 35/741
Bacteria: probiotics
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
C12N 1/20
Microorganisms; Compositions thereof ; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of…:…

Family

Application62/435,048Us provisional application · filed 15 Dec 2016
PCT/US2017/066408Parent of this continuation · filed 14 Dec 2017
Application16/047,862Parent of this continuation · filed 27 Jul 2018
US 2021/0054356 A1Pre-grant publication · published 25 Feb 2021
US 2019/0055529 A1Published application
US 11,254,918 B2This patent

From the US filing history. Foreign family members aren’t listed.