# US 9,752,129 B2 · Host cell modification with artificial endosymbionts

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- Number: US 9,752,129 B2
- Document ID: US9752129B2
- Status: Granted
- Kind: B2
- Application number: 15/331,847
- Filed: 2016-10-22
- Published: 2017-02-09
- Granted: 2017-09-05
- Earliest claimed: 2013-09-03
- Assignees: Bell Biosystems, Inc.
- Applicants: Bell Biosystems, Inc.
- Inventors: Caleb B. Bell, III; Alexey Bazarov; Abdul Wakeel; Joyce Barrozo
- Web page: https://patentgrep.com/patent/US9752129B2

## CPC

- C12N 5/16: Animal cells
- C07K 14/195: from bacteria
- C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C07K 2319/034: containing a motif for targeting to the periplasmic space of Gram negative bacteria as a soluble protein, i.e. signal sequence should be cleaved
- C12N 2510/00: Genetically modified cells
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention is directed generally to host cells with artificial endosymbionts, wherein the artificial endosymbiont and the host cell communicate with each other to alter a phenotype of the host cell. In some embodiments, the communication comprises the secretion of a polypeptide from the artificial endosymbiont into the host cell. The secreted polypeptide can be a selectable marker, a reporter protein, a transcription factor, a signal pathway protein, a receptor, a growth factor, a cytokine, an effector molecule or other factors that can produce a phenotype in the host cell.

## Claims

### Claim 1

An isolated mammalian cell comprising a magnetotactic bacterium, wherein the magnetotactic bacterium provides a protein to the host cell and thereby provides a phenotype to the mammalian cell.

### Claim 2 (depends on 1)

The mammalian cell of claim 1, wherein the mammalian cell is a stem cell.

### Claim 3 (depends on 2)

The mammalian cell of claim 2, wherein the stem cell is a neural stem cell.

### Claim 4 (depends on 2)

The mammalian cell of claim 2, wherein the stem cell is a mesenchymal stem cell.

### Claim 5 (depends on 2)

The mammalian cell of claim 2, wherein the stem cell is a neural crest stem cell.

### Claim 6 (depends on 1)

The mammalian cell of claim 1, wherein the mammalian cell is a neural progenitor cell.

### Claim 7 (depends on 1)

The mammalian cell of claim 1, wherein the mammalian cell is selected from the group consisting of a murine cell, a rat cell, a rabbit cell, a hamster cell, a porcine cell, a bovine cell, a feline cell, a canine cell and a human cell.

### Claim 8 (depends on 7)

The mammalian cell of claim 7, wherein the mammalian cell is a human cell.

### Claim 9 (depends on 7)

The mammalian cell of claim 7, wherein the mammalian cell is a murine cell.

### Claim 10 (depends on 1)

The mammalian cell of claim 1, wherein the protein is a magnetosome protein.

### Claim 11

A method for introducing a phenotype into a mammalian cell, comprising the steps of: culturing an isolated mammalian cell comprising a magnetotactic bacterium, expressing a protein in the magnetotactic bacterium, secreting the protein from the magnetotactic bacterium to the mammalian cell whereby the protein produces a phenotype in the mammalian cell.

### Claim 12 (depends on 11)

The method of claim 11, wherein the protein is a selectable marker.

### Claim 13 (depends on 11)

The method of claim 11, wherein the protein is a reporter protein.

### Claim 14 (depends on 13)

The method of claim 13, wherein the protein is a magnetosome protein.

### Claim 15 (depends on 11)

The method of claim 11, wherein the mammalian cell is stem cell.

### Claim 16 (depends on 15)

The method of claim 15, wherein the stem cell is a neural stem cell.

### Claim 17 (depends on 15)

The method of claim 15, wherein the stem cell is a mesenchymal stem cell.

### Claim 18 (depends on 17)

The method of claim 17, wherein the stem cell is a neural crest stem cell.

### Claim 19 (depends on 11)

The method of claim 11, wherein the mammalian cell is a neural progenitor cell.

### Claim 20 (depends on 11)

The method of claim 11, wherein the mammalian cell is selected from group consisting of a murine cell, a rat cell, a rabbit cell, a hamster cell, a porcine cell, bovine, a feline cell, a canine cell and a human cell.
