US 12,247,064 B2
Modified ligand-gated ion channels and methods of use
Scott Sternson, Chevy Chase, MD (US); Peter Lee, Chevy Chase, MD (US); and Christopher Magnus, Chevy Chase, MD (US)
Assigned to Howard Hughes Medical Institute, Chevy Chase, MD (US)
Filed by Howard Hughes Medical Institute, Chevy Chase, MD (US)
Filed on Jan. 12, 2021, as Appl. No. 17/146,906.
Application 17/146,906 is a continuation of application No. 16/186,122, filed on Nov. 9, 2018, granted, now 10,961,296.
Claims priority of provisional application 62/584,428, filed on Nov. 10, 2017.
Claims priority of provisional application 62/729,716, filed on Sep. 11, 2018.
Prior Publication US 2021/0206831 A1, Jul. 8, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/705 (2006.01); A61K 48/00 (2006.01)
CPC C07K 14/70571 (2013.01) [A61K 48/0008 (2013.01); A61K 48/0058 (2013.01); A61K 48/0066 (2013.01); A61K 48/0091 (2013.01); C07K 2319/03 (2013.01)] 21 Claims
 
1. A method for treating a mammal having a neural channelopathy, said method comprising:
administering a nucleic acid sequence encoding a modified ligand gated ion channel (LGIC) subunit to said mammal under conditions in which said modified LGIC subunit can assemble into a modified LGIC comprising said modified LGIC subunit in a cell within said mammal, wherein each of said modified LGIC subunits comprises:
a human alpha7 nicotinic acetylcholine receptor (α7-nAChR) ligand binding domain (LBD) comprising a L131G amino acid substitution, a Q139L amino acid substitution, and/or a Y217F amino acid substitution as numbered in SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:11, and
an ion pore domain (IPD), wherein the IPD is an IPD from a receptor selected from the group consisting of a serotonin 3 receptor (5HT3) IPD, a glycine receptor (GlyR) IPD, a gamma-aminobutyric acid (GABA) receptor IPD, and an alpha7 nicotinic acetylcholine receptor (α7-nAChR) IPD; and
administering to the subject a LGIC ligand, wherein the LGIC ligand acts as an agonist of said modified LGIC subunit.