US 11,913,019 B2
Compositions and methods for the induction and tuning of gene expression
Pablo Perez-Pinera, Urbana, IL (US); and Charles A. Gersbach, Durham, NC (US)
Assigned to Duke University, Durham, NC (US)
Filed by Duke University, Durham, NC (US)
Filed on Oct. 20, 2017, as Appl. No. 15/789,348.
Application 15/789,348 is a continuation of application No. 14/220,116, filed on Mar. 19, 2014, granted, now 9,828,582.
Claims priority of provisional application 61/803,254, filed on Mar. 19, 2013.
Prior Publication US 2018/0094238 A1, Apr. 5, 2018
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/63 (2006.01); C12N 5/071 (2010.01); A61K 38/17 (2006.01)
CPC C12N 5/0602 (2013.01) [A61K 38/1709 (2013.01); C12N 15/635 (2013.01); C12N 2501/60 (2013.01)] 8 Claims
 
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.