US 11,987,791 B2
Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (HNF4α) gene expression
Jesse Jerome Smith, Waltham, MA (US); Jodi Michelle Kennedy, Dedham, MA (US); Jeremiah D. Farelli, Marblehead, MA (US); Kendrick Alan Goss, Lexington, MA (US); Adam Walter Scheidegger, Somerville, MA (US); Yoseph Kassa, Cambridge, MA (US); Christian Wessel Cobaugh, Newton, MA (US); and Timsi Rao, Allston, MA (US)
Assigned to Omega Therapeutics, Inc., Cambridge, MA (US)
Filed by Omega Therapeutics, Inc., Cambridge, MA (US)
Filed on Sep. 23, 2020, as Appl. No. 17/029,820.
Claims priority of provisional application 62/904,178, filed on Sep. 23, 2019.
Prior Publication US 2022/0348908 A1, Nov. 3, 2022
Int. Cl. C12N 15/11 (2006.01); A61P 1/16 (2006.01); C07K 14/47 (2006.01); C12N 9/22 (2006.01); C12N 15/63 (2006.01)
CPC C12N 15/11 (2013.01) [C12N 9/22 (2013.01); C07K 2319/80 (2013.01); C07K 2319/81 (2013.01); C12N 2310/20 (2017.05)] 37 Claims
 
1. A site-specific hepatocyte nuclear factor 4a (HNF4α) disrupting agent, comprising a site-specific HNF4α targeting moiety which targets an HNF4α expression control region, and wherein the HNF4α targeting moiety comprises a DNA-binding domain of a zinc finger (ZNF) polypeptide, or fragment thereof, that specifically binds to the HNF4α expression control region, wherein the DNA-binding domain of the ZNF polypeptide comprises an amino acid sequence having at least 85% amino acid identity to the entire amino acid sequence of any one of the amino acid sequences selected from the group consisting of SEQ ID NOs: 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, and 159.