	US 11,946,040 B2
	Adenine DNA base editor variants with reduced off-target RNA editing
J. Keith Joung, Winchester, MA (US); Julian Grunewald, Charlestown, MA (US); and Ronghao Zhou, Charlestown, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Filed by The General Hospital Corporation, Boston, MA (US)
Filed on Feb. 4, 2020, as Appl. No. 16/781,979.
Claims priority of provisional application 62/844,717, filed on May 7, 2019.
Claims priority of provisional application 62/800,974, filed on Feb. 4, 2019.
Prior Publication US 2020/0308571 A1, Oct. 1, 2020
Int. Cl. C12N 15/10 (2006.01); C12N 15/113 (2010.01)

CPC C12N 15/1024 (2013.01) [C12N 15/113 (2013.01); C12Y 305/04004 (2013.01)]

19 Claims

1. An adenine base editor (ABE) variant capable of deaminating adenine in DNA comprising an adenosine deaminase and a programmable DNA binding domain, wherein the adenosine deaminase comprises one or more Escherichia coli TadA monomers, wherein each E. coli TadA monomer has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 1 or the amino acid sequence of SEQ ID NO: 34, and wherein at least one of the one or more E. coli TadA monomers comprise one or more mutations at amino acid residue positions that correspond to amino acid residues 10, 11, 13, 21, 25, 26, 49, 58, 71, 72, 74, 77, 82, 109, 111, 122, 128, 129, 139, 140, 143, 148, 150, or 153 of the amino acid sequence of SEQ ID NO: 1 or the amino acid sequence of SEQ ID NO: 34.