# US 12,215,345 B2 · Compositions and methods for the induction and tuning of gene expression

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- Number: US 12,215,345 B2
- Document ID: US12215345B2
- Status: Granted
- Kind: B2
- Application number: 15/789,348
- Filed: 2017-10-20
- Published: 2018-04-05
- Granted: 2025-02-04
- Earliest claimed: 2013-03-19
- Assignees: Duke University
- Applicants: Duke University
- Inventors: Pablo Perez-Pinera; Charles A. Gersbach
- Web page: https://patentgrep.com/patent/US12215345B2

## CPC

- C12N 5/0602: {Vertebrate cells}
- A61K 38/1709: {from mammals}
- C12N 15/635: {Externally inducible repressor mediated regulation of gene expression, e.g. tetR inducible by tetracyline}
- C12N 2501/60: Transcription factors
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Disclosed herein are compositions of transcription activator-like effectors transcription factors and methods of using the compositions for inducing gene expression of mammalian genes.

## Claims

### Claim 1

A method of increasing gene expression of a target gene in a mammalian cell, the method comprising administering to the mammalian cell in vitro two or more transcription activator-like effector transcription factors (TALE-TFs) that bind to at least a first target region and a second target region in the target gene,
wherein at least one of the first target region and the second target region is within a non-open chromatin region,
wherein the first target region or the second target region comprises the nucleotide sequence of one of SEQ ID NOs: 1-28, or the complement thereof,
wherein each TALE-TF consists essentially of a repeat variable diresidue, a transcription activation domain, and a nuclear localization sequence,
wherein gene expression is increased in the mammalian cell, and
wherein the gene expression is increased in the mammalian cell without the use of a chromatin modifying drug.

### Claim 2

A method of increasing gene expression of a target gene in a mammalian cell, the method comprising administering to the mammalian cell in vitro two or more transcription activator-like effector transcription factors (TALE-TFs) that bind to at least a first target region and a second target region in the target gene,
wherein at least one of the first target region and the second target region is within a non-open chromatin region,
wherein each TALE-TF consists essentially of a repeat variable diresidue region, a transcription activation domain, and a nuclear localization sequence,
wherein gene expression is increased in the mammalian cell,
wherein the target gene is IL1RN, KLK3, CEACAM5, or ERBB2, and
wherein the first target region or the second target region comprises a polynucleotide having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-28, or the complement thereof.

### Claim 3 (depends on 2)

The method of claim 2, wherein the TALE-TFs bind to different target regions within the target gene.

### Claim 4 (depends on 2)

The method of claim 2, wherein the gene expression is increased at least 1-fold.

### Claim 5 (depends on 2)

The method of claim 2, wherein the TALE-TFs each comprise the same transcription activation domain.

### Claim 6 (depends on 2)

The method of claim 2, wherein the TALE-TFs each comprise different transcription activation domains.

### Claim 7 (depends on 2)

The method of claim 2, wherein the mammalian cell is a human cell.

### Claim 8 (depends on 2)

The method of claim 2, wherein the gene expression is increased in the mammalian cell without the use of a chromatin modifying drug having an activity selected from the group consisting of histone acetyltransferase, histone deacetylase, histone methyltransferase, and histone kinase activity.